2014 bedside critical care guide

Contents Page #Chapter 2: Management of Common Respiratory Disorders in the ICU: Asthma, Chapter 3: Bedside approach to Gastrointestinal Bleeding in the Intensive Care Unit 13... In thi

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Edited by Ramzy H Rimawi

Bedside Critical Care Guide

Bedside Critical Care Guide

Edited by: Ramzy H Rimawi

Published by OMICS Group eBooks

731 Gull Ave, Foster City CA 94404, USA

Copyright © 2014 OMICS Group

This eBook is an Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications However, users who aim to disseminate and distribute copies of this book as a whole must not seek monetary compensation for such service (excluded OMICS Group representatives and agreed collaborations) After this work has been published by OMICS Group, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work Any republication, referencing or personal use of the work must explicitly identify the original source.

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First published January, 2014

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Critical care medicine is an intriguing, rapidly evolving medical field aimed

to support and restore productive lives in seriously ill patients Critical care specialists often seek up-to-date, evidence-based literature applicable at the patient bedside for common and uncommon disorders encountered in the intensive care unit (ICU) In this review of adult critical care medicine, we provide

a comprehensive guide of bedside ICU principles and best practice standards East Carolina University has a 24-bed medical ICU (MICU), a 24-bed cardiac ICU (CICU), and a 24-bed surgical ICU (SICU) The MICU commonly admits critically ill patients with infectious disease, central nervous system, respiratory, metabolic and endocrine, hematologic, oncologic, gastrointestinal, environmental, obstetric, pharmacologic disorders and renal disorders Our CICU typically admits patients suffering from myocardial infarctions, congestive heart failure, arrhythmias, cardiogenic shock and post-cardiovascular surgical complications The SICU cares for patients with surgical and trauma related conditions.

Currently, critical care is a multidisciplinary specialty that includes many subspecialties of medicine, surgery and anesthesiology I have personally asked the contributing authors of multidisciplinary departments at East Carolina University, including critical care medicine, pulmonology, infectious diseases, nephrology, cardiology, and trauma The contributing authors and I thank OMICS for their assistance is publishing this text

Thank you,

Ramzy H Rimawi

About Editor

Dr Ramzy Rimawi earned his BA in English and Biology at the State University at Stony Brook He then earned his medical doctorate degree from Ross University School of Medicine After completing his Internal Medicine residency training, he pursued a fellowship in Infectious Diseases followed by Critical Care Medicine at East Carolina University for the Brody School of Medicine His passion for critical care lies in its’ rapid physiologic and complex reasoning often in the face of uncertainty His clinical interests are nosocomial infections in the ICU, antibiotic stewardship, infection control and HIV

Dr Ramzy Rimawi has established himself as not only a competent clinician, but also quickly becoming a leader in the field of infectious disease and critical care medicine At a young age he has been very successful in publishing several articles in his field of practice and continues to contribute to the progression of science and medicine He has presented and been recognized for his work

at a national and local level He has board certifications in Internal Medicine, Infectious disease medicine and currently completing his training in critical care medicine.

Bowling Mark

I had the pleasure to work with Dr Ramzy over the past 3 years He is a great example of ambition, dedication, hard working and a great team player His shinning mind has brought our department to a whole new level I have no doubt that he will be an exceptional physician Bringing the critical care to bedside and presenting it in such simplified way to assist other medical providers is a true example of his thrives to provide a better care for patients.

Dr Rimawi has taken a lot of initiatives to help improve the healthcare at our hospital He is very active academically and has worked on multiple research projects and publications The initiative he took to get this eBook published is a testament to his academic inclinations.

The idea of a bedside ICU eBook was excellent, especially with the limited availability of content at the graduate medical education level for residents The book had to be something that was evidence based, concise and practical, and easy to understand I am sure this book meets the above requirements and will

be of great benefit to all.

Nazia Sultana

Ramzy Rimawi and I both did our training in Infectious Diseases together at East Carolina University for the Brody School of Medicine While there, Ramzy has been great mentor that helped oversee my fellowship training as a chief fellow and research career We presented several oral and poster presentations

at national and international conferences together We have successfully published several articles in well-recognized, peer-reviewed journals on topics such as MRSA screening in an ICU setting, tularemia, and infectious disease/ critical care practitioner collaboration But other than being great academic partner, Ramzy and I have been great friends It was an honor to be able to work with him on this e-Book and I look forward to future joint collaborations with him and OMICS.

Kaushal B Shah

I am pleased to write about Dr Ramzy Rimawi I have known Dr Rimawi since July 2013 as a colleague at ECU Brody School of Medicine (BSOM) He has extensive fund of knowledge and practices evidence based medicine He is very well respected as a finest clinician, avid clinical researcher and mentor for fellows/house staff at Vidant Medical Centre.

Dr Rimawi has done a great effort in compiling “Bedside Critical Care Guide”

as excellent evidence based guide for house staff and busy clinicians.

Manjit Singh Dhillon

Dr Rimawi is an outstanding clinician with excellent bedside manners He has demonstrated an ongoing commitment to research as well as teaching, and this book will go a long way in furthering the understanding of critical illness and its management

Abid Butt

It was a great experience for me to write the chapter on scoring systems in critically ill patients I thank Dr Ramzy Rimawi for the opportunity of writing the chapter He is a great physician and person

Ogugua N Obi

The chapters in this eBook include topics from cardiology, nephrology, pulmonary, infectious disease (including sepsis), neuro-critical care, burns, and gastroenterology Highly specialized topics have been left to qualified authors of other specialty texts Each chapter is meant to provide pertinent clinical, diagnostic, and management strategies when caring for critically ill patients The chapters are relatively brief, clinically relevant and evidence-based according to currently accepted literature References are provided for readers wanting to explore subjects in greater detail I have edited and revised the content and style of each chapter so as to unify the voice of the entire text.

Introduction

Contents Page #

Chapter 2: Management of Common Respiratory Disorders in the ICU: Asthma,

Chapter 3: Bedside approach to Gastrointestinal Bleeding in the Intensive Care Unit 13

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Basic Respiratory System Mechanics and Pathophysiology

In the spontaneously breathing patient, downward movement of the diaphragm during inspiration generates negative pressure

in the chest relative to atmospheric pressure, and air moves from the atmosphere into the lungs In spontaneously breathing patients

on mechanical ventilators, positive pressure from the ventilator assists this effort by the patient and reduces the work the patient must do to inhale a given tidal volume In patients who have respiratory failure, the ventilator reduces the work of breathing and

aids in inflating the lungs The work of breathing is related to a pressure-time product, which is the pressure needed to inflate the lungs

multiplied by the time of inspiration For our purpose, we will assume that expiration does not involve significant work by the patient The

pressure which is needed to drive air into the lungs is related to the resistance and compliance of the system Resistance is increased by narrowing of the airways or narrowing of the endotracheal tube, which can occur if a patient bites on the tube or secretions collect on

the inside Calculation of resistance, which modern ventilators can estimate, is related to Δ pressure/Δ flow (R= ΔP/ΔFlow) Compliance

is simplistically understood as the work needed to inflate a balloon Stiff balloons like stiff alveoli require more pressure to inflate Compliance = Δvolume/Δpressure [1] Compliance is the opposite of elastance, thus alveoli with high elastance have low compliance There are 2 components of compliance: compliance related to the alveoli and compliance related to the chest wall Diseases which cause low compliance of the lungs include fibrosis, interstitial edema, and pneumonia Conditions in which there is low chest wall compliance include abdominal distention, pleural effusion, or obesity The following image demonstrates how at low lung volumes compliance is low, but as the lungs are inflated compliance increases

Figure 1: Compliance in Relation to Pressure and Volume

It is also important to know that diseased lungs are heterogeneous, and there are areas with low compliance (severely injured areas) and high compliance (emphysema), and also areas with high resistance (bronchospasm) and less resistance If the physician orders a high tidal volume to be delivered by the ventilator, that volume may go mostly to the more compliant (normal) part of the lung and cause over distention and injury to that part of the lung This is called volutrauma and is why lower tidal volumes (6-8 mL/kg/IBW) are recommended in patients with ARDS Lower tidal volumes (i.e 4 mL/kg/IBW) have also been described) Positive end expiratory pressure (PEEP) is used to inflate the lungs and usually improves the compliance by putting the lung in a more favorable place on the pressure volume curve seen in Figure 1 [2] A sudden drop in compliance would be manifested by the ventilator graphics showing a higher pressure at the end of both inspiration and expiration and sudden drop in tidal volumes This could be seen with a pneumothorax

Robert A Shaw *

Critical Care & Sleep Medicine, Section of Pulmonary, Department of Internal Medicine, Brody School of Medicine, East Carolina University, USA

*Corresponding author: Robert A Shaw, Critical Care & Sleep

Medicine, Section of Pulmonary, Department of Internal Medicine, Brody School of Medicine, East Carolina University, Brody 3E-149, Greenville, NC 27834, USA, Tel: 252-744-4650

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Mechanical Ventilation Principles

As mentioned above, a mechanical ventilator assists breathing and inflates lungs by delivering oxygen enriched air into the lungs The ventilator will target either pressure or volume in doing this In spontaneously breathing patients, each breath will be triggered by

a change in pressure or flow in the circuit Each inspiration will be cycled off by either a time limit or decrease in flow Let us make this terminology understandable so that you will know what different modes of ventilation mean

A Volume targeted ventilation: When patients are intubated, usually a volume targeted mode is initiated This is because you

would like to assure that the patient is receiving an adequate tidal volume with each breath In volume targeted ventilation, the therapist

“tells” the ventilator to deliver a given volume, say 500 ml The therapist sets a flow rate and the machine delivers the gas at that flow rate until the desired volume is given The machine times how long it takes to give that volume This is commonly called assist control mode (AC) In more modern ventilators, a microprocessor looks at previous breaths, and if they have been below the target, it will increase the pressure and inspiratory time to reach the targeted tidal volume An example of this mode is: pressure regulated volume control (PRVC)

or sometimes called APV-CMV With this mode of ventilation, the patient can trigger the breath or if the patient has no drive to breath

a back- up rate is set to insure that a minimum number of breaths occur each minute

B Pressure targeted ventilation: In this mode, the therapist “tells” the ventilator to deliver the gas at a given inspiratory pressure

above the PEEP Breaths are generated by the patient or the machine and the machine then delivers the gas with a high flow rate until the targeted pressure is achieved Note that there is no guarantee of a set tidal volume If compliance drops or resistance increases, the patient will receive a lower tidal volume Examples of pressure targeted modes are: pressure support ventilation (PSV), pressure control (PC), and airway pressure release ventilation (APRV) In reality, when a therapist is doing PSV, the inspiratory pressure is set so the patient receives tidal volumes that are comfortable for the patient The work of breathing is reduced and the patient breaths with a lower respiratory rate For example, if a patient is tachypneic with low tidal volumes on PSV, the therapist would usually increase the pressure support so the patient receives higher tidal volumes and becomes less tachypneic It is important to realize that with PSV, the patient must trigger each breath, and this mode is not appropriate for patients who have no drive to breath or cannot generate a breath due to paralysis Pressure control mode is a mode in which the therapist sets the time for inspiration and expiration Patients are heavily sedated or paralyzed

C Airway pressure release ventilation: Another pressure targeted mode, which is often used in patients with ARDS, is airway

pressure release ventilation (APRV) This mode is similar to having a patient on continuous airway pressure (CPAP) with intermittent drops in the pressure APRV holds the alveoli inflated (during P HIGH), except for the brief releases (P LOW) and recruits (opens) alveoli similar to higher PEEP, as illustrated in Figure 2 [3] It is used to reduce shunt and improve oxygenation in patients with ARDS The following graphic illustrates the physiology of APRV:

Figure 2: Airway pressure release ventilation vs Conventional Volume-Targeted Ventilation

D Combined pressure and volume targeted ventilation: Some ventilators can target either pressure or volume with delivered

breaths An example of this is synchronized intermittent mandatory ventilation (SIMV) In this mode, some breaths are triggered by the patient initiating a breath and some are time cycled by the ventilator The therapist “tells” the ventilator to give a minimum number

of breaths/minute These are the intermittent mandatory breaths, and they are volume targeted The ventilator also allows the patient to trigger breaths spontaneously and these breaths are pressure supported Graphically this is shown in Figure 3:

Figure 3: Synchronized Intermittent Mandatory Ventilation.

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If the ventilator is set on SIMV mode and the therapist “tells” the machine to do 6 intermittent mandatory breaths/minute with tidal volume 400 cc and pressure support of 15 cm H2O, then the patient will receive a 400 cc tidal volume every 10 seconds synchronized with the patient’s effort Other patient initiated breaths will be pressure support breaths with 15 cm pressure

Positive End Expiratory Pressure (PEEP)

PEEP is the pressure that the ventilator maintains at the end of exhalation When you see a patient with COPD doing pursed lip breathing, he/she is exhaling against “pursed lips”, which is creating a small amount of PEEP PEEP helps to prevent atelectasis and also opens previously closed alveoli It “recruits” alveoli and can improve oxygen entering into the capillaries supplying those alveoli Increasing PEEP will usually improve compliance (unless the lung is over distended) and improve oxygenation It also helps to reduce

“atelectrauma”, which is lung injury caused by repeated closure and opening of alveoli There are tables which help in setting the amount

of PEEP to use but in reality, most physicians gradually increase PEEP so that the inspired FiO2 is <0.6 with a pO2 >60 In patients with very low compliance, such as severe obesity, higher PEEP is really effective in opening the lungs and improving oxygenation In ARDS patients PEEP is often as high as 20 cm H2O and in obese patients PEEP is sometimes as high as 30-35 cm H2O Some centers insert an esophageal balloon in patients in order to measure transpulmonary pressure (TPP) and set the PEEP high enough so that TPP is positive

Weaning from Mechanical Ventilation or “Liberation from Mechanical Ventilation”

Assuming that the underlying cause of the respiratory failure has been improved, one then considers transition to having the patient assume more of the work of breathing and ultimately being “liberated from mechanical ventilation.” Spontaneous breathing trials (SBT) are conducted to evaluate the readiness of the patient to be extubated Before starting an SBT, the patient should be alert and able to follow simple commands The patient should be adequately oxygenated with FiO2 of 0.4 or less and PEEP should be <10 The exception to this

is in obese patients, who often are on higher PEEP amounts to maintain inflation of the lungs Usually patients are on pressure support mode and respiratory rate is <24 before considering an SBT Most physicians and therapists will calculate the rapid shallow breathing index (respiratory rate/tidal volume) and if <105 it is reasonable to do an SBT An SBT means the patient is on minimal PS (5 cm H2O)

or just on T Bar (oxygen but no positive pressure) A successful SBT means the patient breaths spontaneously for >30 minutes with respiratory rate <35 breaths/minute, O2 sat> 90%, heart rate increase of <20%, no significant change in blood pressure, and no severe anxiety Before removing the tube, the patient should be able to protect the airway and clear secretions effectively If the patient fails the SBT, then he/she is placed back on mechanical ventilation (usually PS mode) for 24 hours and the underlying problems are addressed further This often requires diuresis and/or antibiotics to treat an infection Patients with COPD sometimes fail the SBT because of weakness of the respiratory muscles, and they should be rested on adequate PS so that they are not tachypneic

Noninvasive Positive Pressure Ventilation NIPPV

This refers to positive pressure ventilation via a mask rather than insertion of an endotracheal tube Endotracheal intubation can have the following complications: trauma to airway, infection due to bypassing the airway defenses, discomfort, need for sedation and pain control While NIPPV can be uncomfortable, it reduces the risks of intubation NIPPV, sometimes simply called noninvasive ventilation (NIV), can deliver a fixed pressure CPAP or a higher pressure during inspiration than during expiration (BIPAP bilevel pressure) CPAP

is used to treat diseases where the problem is simply oxygenation, such as pulmonary edema BIPAP is used when there is a problem of both ventilation and oxygenation, such as COPD, neuromuscular disease like amyotrophic lateral sclerosis, or obesity hypoventilation syndrome

NIPPV has improved outcomes in patients with obstructive disease such as COPD It has also been beneficial in restrictive chronic diseases such as kyphoscoliosis, obesity hypoventilation syndrome, and neuromuscular disease (amyotrophic lateral sclerosis) It also has helped in patients with extubation failure There are many contraindications to NIPPV including hemodynamic instability, respiratory arrest, excessive secretions, agitated, unable to fit mask, or recent airway surgery It can be time consuming for respiratory care practitioners to work with the patient to help him/her get used to the device and find the right mask Frequent assessment of the patient is important, and if the patient is not breathing with a slower rate and improved oxygenation and ventilation after 2 hours, then intubation will probably be necessary

An Ideal patient, who would benefit from short term CPAP, would be one who comes to the emergency department with acute pulmonary edema and needs help with oxygenation until diuresis occurs Typically a pressure of 10-12 cm H2O is used An ideal patient, who would benefit from BIPAP would be one with COPD exacerbation and labored breathing that is hypercapnic BIPAP at 14/8 cm H2O would help reduce the work of breathing while bronchodilators and steroids start working A COPD patient who is extubated and

is working hard to breath might also benefit by avoiding re-intubation There are complications from NIPPV including: mask discomfort, air leaking, aspiration, failure to ventilate, and pneumothorax Patients should always have head of bed elevated and be monitored with oximitry and EKG

Cases to Illustrate Common Ventilator Related Problems

Case 1: A patient with COPD has been converted from a volume targeted mode to a pressure targeted mode, pressure support The

therapist places the patient on PS 12/5 cm pressure with FiO2 of 0.4 The patient has a RR of 35 breaths/minute, O2 sat is 93%, and tidal volumes are 200 cc-260 cc Arterial Blood Gas: pCO2 45, pO2 75, pH 7.38 What would you recommend?

Case 2: A patient with diffuse infiltrates caused by sepsis and fluid resuscitation is on a volume targeted mode, PRVC The ventilator

has the following settings: target tidal volume 400 cc (6 cc/kg IBW), FiO2 0.8, set rate 8/minute, PEEP 20cm H2O ABG: pCO2 38, pO2

50, sat 82%, pH 7.36 What options do you have?

Case 3: A patient with COPD is on a volume targeted mode, PRVC Target tidal volume is 500cc, FiO2 0.4, PEEP 5 He has become

very tachypneic and is fighting the ventilator You notice that he is trying to breathe with his abdomen protruding 40 times per minute but the ventilator is only delivering 20 breaths/minute The following graphic is noted (the patient in blue, normal in red) Why is the patient not getting a breath with every effort? What is the problem?

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Figure 4: Graphic for Case 3

Case 4: A patient was on volume mode, PRVC, and was improving so you decide to put him on pressure support mode (PSV) to see

if he could do a spontaneous breathing trial and be weaned On the PRVC mode, the set rate was 14/breaths/minute and the patient was breathing 14 breaths/minute ABG: pCO2 34 pO2 70 pH 7.48 After being placed on PSV, the nurse calls and reports the patient has long apnea periods What is the problem and what would you do?

Case 5: A patient is on PRVC mode and suddenly becomes tachypneic and airway pressures increase The ventilator graphic

shows that the difference between the peak airway pressure and the plateau pressure (pressure when expiratory hold is prolonged) has decreased significantly This is shown below:

Figure 5: Graphic for Case 5.

Discussion of Cases 1-5

Case 1: This COPD patient is very tachypneic with low tidal volumes on PSV 12/5 Many events could cause tachypnea, including

pulmonary embolism, sepsis, pneumothorax, or metabolic acidosis The most often cause of this, however, would be that the patient is

not getting enough help from the ventilator Patient needs more pressure support After examining the patient, it would be appropriate

to increase the PS to 16 and see if that corrected the tachypnea and labored breathing Remember that with mechanical ventilation, we are trying to partially unload the breathing muscles but do not want to excessively work them It is not known exactly how much work

to impose on the patient, but tachypnea (RR>30) often is a sign of fatigue of respiratory muscles Exhausting the muscles will prolong weaning in a COPD patient

Case 2: This patient has severe ARDS with a pO2/FiO2 ratio of 62 Patient has hypoxemia with low oxygen saturation, and that will

reduce oxygen delivery to the tissues You would like to increase saturation to >90% Option 1 would be to increase the FiO2, but that

is not the best option because of potential oxygen toxicity You would like to “recruit lung” in order to better oxygenate the patient and reduce FiO2 Since the patient is already on 20cm PEEP, which is about as high as is generally done (except in patients with obesity or low chest wall compliance), raising the PEEP further is not a good option This is a situation where changing the mode to airway pressure release ventilation (APRV) would be appropriate On this mode, the mean airway pressure would increase and areas of collapsed alveoli would open up Changing to this mode will often reduce the shunt fraction and oxygenation of blood will improve This often takes 6-12 hours to work, so do not expect immediate improvement in ABG You may want to also increase the FiO2 temporarily to insure adequate oxygenation of the patient The respiratory care practitioner will help in deciding the best P high and P low

Case 3: You should note on the graphic that even at the end of exhalation, the patient has flow continuing In a normal patient, all

of the air is exhaled and flow goes to 0 at end exhalation When there is continuing flow at the end of exhalation, which means there is air trapping and auto-PEEP Auto Peep means there is pressure in the alveoli at the end of expiration because not all of the inspired gas was exhaled Remember that in order to trigger the ventilator the patient must generate about 2 cm of negative pressure below the set PEEP If, for example, there is 6 cm of auto-PEEP the patient will have to generate negative 8cm pressure to trigger the next breath In a hyper-inflated COPD patient that may be impossible This patient is not triggering the ventilator due to auto-peep The solution to this includes bronchodilators, reducing the tidal volume, sedation of patient to slow the respiratory rate and allow more time for exhalation,

or increasing the inspiratory flow rate so as to give longer exhalation time [4] When auto-peep is severe, it is best to disconnect the patient from the ventilator to let trapped air to escape and bag the patient for a few minutes

Case 4: On the PRVC mode this patient is on a rate of 14 This is really a back-up rate meaning the patient will receive a minimum

of 14 breaths/minute, even if the patient is apneic This patient is “riding the rate” and is not breathing over the rate The ABG indicates respiratory alkalosis, which will reduce the drive to breath When the patient is changed to PSV, there is no back up rate, and since the drive to breath has been reduced by the respiratory alkalosis, the patient has apneas You could just let the apneas continue and the patient’s pCO2 will rise, and then the patient will have increased ventilatory drive Another option would be to put the patient back on the PRVC mode but decrease the rate to a more appropriate rate, say 6 The patient will eventually start breathing over the rate and then

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can be put back on PSV In patients like this narcotics/sedatives should be reduced because that can cause apneas In a few patients, too much oxygen can reduce drive to breath, and FiO2 should be reduced This is often the case in obesity hypoventilation syndrome patients

Case 5: It is important to know that airway resistance is related to the difference between the peak airway pressure and the plateau

pressure In this graphic that difference is higher in the graphic on the left (patient in trouble) than the graphic on the right (patient doing well) Thus the patient in trouble on the left has higher airway resistance than the patient on the right, possibly due to bronchospasm or mucous in the endotracheal tube In this case, you would be sure the tube is clear and it is easy to pass suction catheter Bronchodilators would help if there is wheezing and bronchospasm If both the peak pressure and plateau pressure suddenly increase by the same amount, then there has been a drop in compliance (pneumothorax could cause that)

Summary

Respiratory failure usually occurs because there is high airway resistance or low compliance Less common is decreased drive to breath, such as with benzodiazepine or narcotic ingestion The high work of breathing can be relieved by either non-invasive positive pressure ventilation, NIPPV (COPD exacerbation or pulmonary edema), intubation with volume targeted mode (assist control or PRVC), or intubation with pressure targeted mode (pressure support or airway pressure release ventilation) Positive end expiratory pressure (PEEP) is used to recruit alveoli and improve oxygenation When the underlying problem has been corrected, the patient should

be evaluated for liberation from mechanical ventilation with a spontaneous breathing trial

References

1 MacIntyre NR, Branson RD (2009) In: Mechanical Ventilation (2ndedn), Saunders Elsevier, St Louis, USA

2 Berne RM, Levy MN (1999) In: Berne & Levy Principles of Physiology (3rdedn), Mosby, USA

3 Habashi NM (2005) Other approaches to open-lung ventilation: airway pressure release ventilation Crit Care Med 33: S228-240.

4 Dhand R (2005) Ventilator graphics and respiratory mechanics in the patient with obstructive lung disease Respir Care 50: 246-261.

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Management of Common

Respiratory Disorders in the ICU:

Asthma, COPD, and ARDS

Source of Funding/Conflicts of Interest: Author Mark A Bowling has a potential conflict of interest

with Covidien Surgical Solutions (consultant) Covidien Surgical Solutions was not involved in the production of this manuscript

Dr Hunter Coore does not have financial disclosures to report None of the authors have received any source(s) of funding for this manuscript The corresponding author, Mark A Bowling, had full access to all the data in the study and had final responsibility for the decision to submit for publication

Abstract

Pulmonary disorders are frequently encountered in the intensive care unit (ICU) Complications of asthma, chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS) are three of the most common respiratory disorders faced

by the ICU physician This chapter will focus on the basic ICU management for these pulmonary disorders

Keywords: ARDS; Asthmaticus; COPD exacerbation; Hypercapnia; Status respiratory failure

Introduction

Respiratory disorders are a common problem faced in the intensive care unit In this section we will discuss three of the most common pulmonary disorders seen in critical care medicine; this includes chronic obstructive pulmonary disease (COPD) exacerbation, acute asthma, and acute respiratory distress syndrome (ARDS)

Chronic Obstructive Pulmonary Disease Exacerbation

Background

Chronic obstructive pulmonary disease (COPD) is characterized by persistent non-reversible airflow obstruction due to destruction

of the distal airways from local inflammation as a result of exposure to noxious particles and gases (mostly from tobacco abuse) This permanent change in lung structure coupled with chronic inflammation leads to a progressive decline in lung function, abnormal gas exchange, pulmonary hypertension, air trapping (inability to deflate the lung), increased sputum production, skeletal muscle wasting and cachexia [1] The Global Initiative for Chronic Obstructive Lung Disease (GOLD guidelines)defines COPD as a ratio of forced expiratory volume in 1second (FEV1) over forced vital capacity<0.70 (FEV1/FVC<0.70) [1] The severity of airflow obstruction measured by spirometry is based on the measurement of the FEV1:

Stage 1 = mild (FEV1>70 ml)

Stage 2 = moderate (FEV1 50-70 ml)

Stage 3 = severe (FEV1 30-50 ml)

Stage 4 = very severe (FEV1 <30)

The Center for Disease Control and Prevention (CDC) in 2011 reported that COPD was the third leading cause of death in the United Statesand approximately fifteen million people have been diagnosed with the disease [2] It is has been predicted that in 2020

it will be the 3rd leading cause of mortality worldwide and the 5th leading cause of burden of disease [3,4] Many of the patients that are diagnosed with COPD will have acute symptoms of the disease termed exacerbations In the United States, acute exacerbations of COPD (AECOPD) are responsible for about 500,000 admissions to the hospital yearly, with half of these admissions requiring ICU level care [4] The mainstays of therapy for AECOPD include the maintenance of adequate oxygenation and ventilation, bronchodilator therapy, corticosteroids and antibiotics [5] Below we will describe the definition, risk factors and therapy in the care of patients with these exacerbations

Mark A Bowling 1 * and Hunter A Coore 2

Carolina University, Greenville, USA

Carolina University, Greenville, USA

*Corresponding author: Mark R Bowling, Assistant Professor

of Medicine, Brody School of Medicine - East Carolina University, Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, 3 E-149 Brody Medical Sciences Building, 600 Moye Blvd., Mail Stop 328, Greenville, NC, USA, Tel: 278834-4354;

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Definition and risk factorst

COPD exacerbations are defined by the GOLD criteria as an increase in the frequency or severity of a cough, worsening dyspnea and

a change in character or volume of sputum production [1] There are several identifiable predictors for patients at risk for COPD, which include: the duration of COPD diagnosis, number of hospitalizations, sputum production, steroid use, antibiotic use, and co-morbidities (cardiovascular disease) [6] Additionally, those with GOLD Stage 3-4 are at an increased risk for exacerbations [1]

Clinical presentation and initial evaluation

Patients experiencing an AECOPD may present with several complaints and symptoms, including increased dyspnea and cough, worsened hypoxemia, hypercapnia (resulting in an acute metabolic acidosis), mental status changes, and symptoms related to a primary issue such as pneumonia, cardiovascular events, arrthymias, and organ failure [7] Many of these patients will require ICU admission [7] The initial approach in the care of these patients starts with a history and physical examination focusing on potential causes of the exacerbation (infections, cardiac events) and evidence of impending respiratory failure It is important to remember that many of these patients will have significant co-morbidities, which may add to the complexity of the situation For example, it is rare that a patient with COPD and heart failure will present with just heart failure or COPD symptoms alone, it is usually a combination of both Therefore, both problems need to be addressed A quick evaluation of the patient’s ability to maintain adequate oxygenation and ventilation is necessary and pertinent The following may help in this assessment:

• Oxygen saturation <88% on room air

• Use of accessory muscles

• Increase respiratory rate

• Inability to talk clearly due to difficulty breathing

• Mental status changes and evidence of inability to adequately protect the airway (i.e decrease gag reflex)

• Arterial blood gas demonstrating hypoxia and hypercapnia with an acute respiratory acidosis

If there is concern that the patient cannot adequately protect the airway or experiencing significant hypercapnic respiratory failure, either endotracheal intubation or non-invasive mechanical ventilation should be considered immediately If airway protection is of a concern, non-invasive mechanical ventilation should not be utilized Other studies to consider include a chest roentogram (to evaluate for lung parenchymal abnormalities such as pneumonia, pneumothorax, or pulmonary edema, etc.), measurement of arterial blood gas, and appropriate studies focusing on the underlying cause of the exacerbation

Mechanical ventilation and Oxygen therapy

Non-invasive mechanical ventilation: Most patients with acute respiratory failure from a COPD exacerbation can be managed with

non-invasive positive pressure ventilation (NIPPV) NIPPV is considered first-line therapy for patients with COPD exacerbations that have acute hypercapnic respiratory failure and no contraindications to NIPPV [1] Several studies have reported improvement in clinical outcomes such as a decrease in mortality, need for intubation, treatment failure, improvement in respiratory failure, and decreased respiratory rate [8] It is unclear as to what initial settings one should consider when treating these patients An approach can be to place these patients on a bi-levelventilator mode, triggered by spontaneous breathing The inspiratory pressure is initially started at 10-12 cm

H2O and expiratory pressures at 5 cm H2O The inspiratory pressure is adjusted to ensure comfort and ventilator synchrony The goal of therapy is to relieve the work of breathing and increase ventilation Attempt to correct the hypercapnia by following the change in pH to near normal levels and not to a normal pCO2, since a majority of these patients have a baseline chronic hypercapnia

Invasive mechanical ventilation: Some AECOPD patients, based on clinical judgment, require endotracheal intubation and

mechanical ventilation to maintain adequate oxygenation and ventilation There are several different strategies for managing patients on

a mechanical ventilator with COPD and it is unclear if which particular strategy is best However, it has beenwell describedthat liberation from the ventilatorshould begin early to prevent muscle atrophy

Oxygen therapy: Oxygen therapy and smoking cessation remainsa corner stone of COPD treatment Best practices with oxygen

therapy are to observer the arterial hemoglobin saturation with pulse oximetry and maintain the level of approximately 90%, commonly between 88-92%, but not higher [4]

Pharmacologic therapy

Bronchodilators: Short acting inhaled anticholinergic agents (i.e ipratropium) and beta-agonist (i.e albuterol) are the main

stay of therapy for AECOPD Although they can be given separately or in combination solutions, several studies have demonstrated thesignificant bronchodilatation when these agents are givenconcomitantlyversuseither agent being given alone [9-11] These agents have

a rapid onset and can be administered in a nebulizer fashion or a metered dose inhaler (MDI) (Table 1) Evidence suggests that there is

no difference in the efficacy between nebulizer versus MDI with a spacer in the delivery of inhaled medication [1] In the acute setting, the nebulizer method may be easier for the patient to administer [1]

Ipratropium bromide 1) MDI: 18 mcg 2 puffs with spacer every 4 hours

2) Nebulizer: 500 mcg every 4 hours Albuterol 1) MDI: 90mcg four puffs every 4 hours with a spacer

2) Nebulizer: 2.5 mg (dilute to 3 ml) every 4 hours Ipratropium bromide & albuterol combination 1) MDI: (90 mcg albuterol/18 mcg Ipratropium) 2 puffs with a spacer every 4 hours

2) Nebulizer: (2.5 mg albuterol/0.5 mg ipratropium) in 3 ml vial every 4 hours

Table 1: Common dosing regimens in AECOPD

Glucocorticoids: Systemic corticosteroids have been shown to improve symptoms, lung function, and decrease hospital length of

stay [1,12] The optimal dose and duration of glucocorticoids is unknown and may depend on the patient’s response to therapy While the consensus in the literature favors a moderate dose of steroids (30 to 40 mg daily), this may not pertain to critically ill patients [1] Evidence suggests oral administration is just as efficacious as an intravenous route [13] A commonly prescribed agent is 125 mg of methylprednisolone every 6 hours for 72 hours followed by a 2-week oral taper starting at 60 mg [8] Prolonged treatment leads to increased adverse reactions from corticosteroids without improving efficacy, morbidity or mortality [12-15] Hence, shorter tapering regimens have been suggested starting witha standard 3-day intravenous regimen noted above followed by a 30 mg dose for 5-10 days

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Antibiotics: There is a large and consistent beneficial effect of antibiotics in AECOPD patients admitted to an ICU [16] Typical

bacteria isolates recovered in AECOPD patients include Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis

[17] While mild-moderate AECOPD is usually treated with a conventional broad-spectrum agent (i.e doxycycline, sulfamethoxazole and amoxicillin-clavulonate potassium), severe AECOPD usually includes a 3rd generation cephalosporin (i.e ceftriaxone) in combination with a macrolide (i.e azithromycin) or a fluoroquinolone (i.e moxifloxacin) Agents may be changed based

trimethoprim-on community or institutitrimethoprim-onal antibiogram and resistance patterns While it may not provide efficacy in the ICU setting, influenza and pneumococcal vaccines should be considered prior to hospital discharge

Asthma

Background

Asthma is a chronic inflammatory disease of the airways similar to COPD in that patients typically have recurrent respiratory symptoms such as cough, chest tightness, dyspnea and wheezing The pathophysiology of asthma includes airway inflammation, hyper-responsiveness, and remodeling resultingin completely reversible airflow obstruction either spontaneously or with therapy.The severe airflow obstruction can result from bronchial constriction, edema, and/or secretions from inflammation In turn, this can lead

to air trapping (increasing intrathoracic pressure), hypercapnia, hypoxemia, and an increase in the work of breathing If not treated appropriately, the airflow obstruction can be permanent as a result of this alteration of the bronchial mucosa

The CDC reports that 1 in every 12 adults have asthma in the US [18] In the 2009, there were 1.9 million adult and child emergency department (ED) visits as a result of asthma, of which 479,000 required hospital admission and 3,388 died (an age-adjusted death rate

of 1.1 per 100,000 population) [19] Like COPD, asthma can have acute worsening of symptoms (exacerbations) and require ICU admission The major risk factors for a patient suffering from severe asthma include a slow onset of symptoms [20] and prior history of poorly controlled or near fatal asthma [21-23]

Clinical presentation and initial evaluation

On physical exam you may find the patient in significant respiratory distress with inability to talk in full sentences or lie flat An increase in the respiratory rate is often observed with use of accessory muscles Pulsus paradoxicus (a significant decrease in systolic blood pressure upon inspiration) is often present in severe cases as a result of an increase in the intrathoracic pressure from air trapping

A chest roentogram may demonstrate hyperinflation and peak flow measurements may be significantly decreased from the patient’s baseline values

Pharmacologic therapy

The goal of therapy is to quickly reverse the significant airflow obstruction and inflammation with bronchodilators and glucocorticoids, respectively

Inhaled beta-agonist: Short-acting β-receptor agonists (i.e albuterol) are the drugs of choice in acute asthma exacerbations and

quickly cause bronchial smooth muscle relaxation [24] Long-acting beta-agonist is not typically used in these acute cases Inhaled MDI or aerosol delivery is preferred over oral or intravenousroute due to improved efficacy [25-27] There does not appear to be any difference in efficacy between the nebulized versus MDI with a spacer administration [28] When giving these therapies one needs to be mindful of the side effects of the β-receptor agonists in high doses, these include tachycardia, tremor, and hyperglycemia and decreased serum potassium Dosing can either be recurring/cyclic or continuous: repetitive nebulizer treatments (2.5-5 mg dose) or in the case of ventilated patient’s repetitive use of MDI (4-8 puffs of 90 μg of albuterol per puff); continuously given as 1-hour nebulizer treatments using 10-15 mg of albuterol

Anticholinergic therapy: Inhaled anticholinergic agents (i.e., ipratropium) are recommended for acute asthma inED, but not

hospitalized, patients [29] However, many studies have suggested that the combination of inhaled anticholinergics and beta-agonists be utilized in ED patients with severe airflow obstruction since this combination results in a greater bronchodilation than either drug alone [10,30,31] When using ipratropium in combination with albuterol, the dosing is 0.5 mg every 20 minutes x 3 doses then every 2 to 4 hours as needed (nebulized) If using an MDI, the dose is 4-8 puffs (18 μg per puff) in the same regimen

Systemic steroids: The goal of using corticosteroids is to help reduce inflammation It may take a few hours before it is effective and

therefore, the quick relief of bronchoconstriction by a short-acting beta-agonist and anticholinergic is important Systemic steroids may help improve long-term recovery by decreasing airways inflammation Steroids are recommended in patients with severe acute asthma and should be administered intravenously [29] Based on expert opinion [32], the dosing should include intravenous methylprednisolone (60-80 mg every 12 hours) followed by a transition to10-14 day course of oral steroids when the patient can tolerate oral medications

Magnesium sulfate: Magnesium sulfate (2 grams administered IV over 20 minutes) may be helpful in acute asthma due to its ability

to relax bronchial smooth muscle [33] Its use is recommended to patients with severe symptoms that have not resolved after one hour

of aggressive conventional therapy [29]

Respiratory failure

Approximately 4% of hospitalized asthmatics develop significant respiratory failure that requires endotracheal intubation and mechanical ventilation [34] This can be a very challenging problem to manage as they can develop various complications from securing the airway to barotrauma from the mechanical ventilation In this section, we will highlight some of the basic ICU principals in the airway management and ventilation strategies for the patient with respiratory failure due to acute asthma

Airway management: The decision to intubate is based on clinical judgment based on the patients’ ability to protect their airway

and maintain adequate oxygenation with supplemental oxygen and NIPPV It is important to remember that the patient’s respiratory issues can continue post-intubated and adding a mechanical ventilator may further complicate the problem It is highly recommended that experienced physicians and respiratory therapists treat patients with acute asthma Additionally, it is also recommended that the healthcare provider performing the intubation be experienced and trained in the management of patients with potentially difficult airways

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Non-invasive mechanical ventilation: NIPPV is an excellent option for patients that do not require immediate endotracheal

intubation or have a contraindication to NIPPV therapy [35-39] Typically, a bi-level mode with inspiratory pressure starting at 10-12

cm H2O and expiratory pressures of 5-8 cm H2O is used and adjustments are made to increase ventilation and work of breathing Of importance is that if NIPPV is utilized, frequent monitoring is necessary for response to therapy and a declining respiratory status NIPPV should not be a substitute for the patient that requires endotracheal intubation and mechanical ventilation

Invasive mechanical ventilation: Due to the physiologic consequences of significant airway constriction (airflow obstruction,

hypoxia, hypercapnia, air trapping) in asthmatic patients, the ventilator management can be very challenging and may result in complications General principles to consider in the ventilator management of these patients include dynamic hyperinflation as a result

of a prolonged expiration from constricted airways This can be made worse by mechanical ventilation if the respiratory rate is not spaced far enough apart allowing the inhaled gas time to escape before a second breathe is administered This can cause a tremendous amount of pressure in the chest, resulting in hypotension from a decrease in blood return to the right heart, worsening hypercapnia, and barotrauma (pneumothorax, pneumomediastinium, etc.)

Strategies to decrease hyperdynamic inflation include [40]:

• Increase the ventilator flow rate in order to decrease the inspiratory time and increase the expiratory time

• Decrease the respiratory rate, allowing the inhaled gas time to be exhaled

• Decrease the tidal volume, allowing less inhaled gas to be exhaled

Adjunctive therapies: In some severe cases when oxygenation and ventilation cannot be achieved by conventional methods, other

therapies have been utilized in the management of acute asthma Listed below is a brief description of these therapies We recommend that only those physicians that are familiar with the utility of these agents should administer these treatments

i Heliox Therapy

Heliox is the blend of helium and oxygen that can be helpful by enhancing the delivery of oxygen and inhaled medication to the distal airway in acute asthmatics [41] It has a density less than air and can overcome the significant airway resistance in these patients [41-44]

ii General Anesthesia

Several different agents such as ketamine and isoflurane have been used in the management of these patients mostly due to their bronchodilatation properties [45-47]

Acute Respiratory Distress Syndrome

Clinical presentation and initial evaluation

The initial signs of ARDS are tachypnea and progressive hypoxemia Physical exam may reveal manifestations of the initial insult such as pneumonia, sepsis or trauma Typically, the patient will have an increased respiratory rate, use of accessory muscles and diffuse crackles upon auscultation of the lungs There may be signs of peripheral cyanosis and poor perfusion if shock is present The chest roentogram is often unrevealing in the first few hours, but will eventually show dense bilateral infiltrates As the disease progresses, the patients’ hypoxemia often progresses to require mechanical ventilation

Appropriate laboratory and radiologic studies should be directed to the underlying disease For example, if pneumonia is suspected, blood and sputum cultures may be appropriate If the patient had significant trauma, radiologic studies should be directed to evaluate the extent of the injury It is imperative to evaluate the arterial oxygen and carbon dioxide tension with arterial blood gas monitoring

in all these patients

Diagnosis

In 2011, an expert panel from an initiative of the European Society of Intensive Care Medicine endorsed by the American Thoracic Society and the Society of Critical Care Medicine developed the Berlin definition of ARDS [52] According to the Berlin ARDS definition, all of the following criteria must be met:

• Respiratory symptoms must occur or become worse within one week of the initial insult

• Bilateral pulmonary opacities consistent with pulmonary edema on radiographic imaging (not be due to pleural effusions, lobar

or lung collapse, or pulmonary nodules)

• The respiratory failure must not be due to cardiac failure or volume overload This must be verified by an objective measure

such as (echocardiogram, pulmonary occlusion pressure, etc.) to exclude hydrostatic pulmonary edema if there is no risk factors explain the ARDS

• Impaired oxygen exchange must be present as defined by the ratio of arterial oxygen tension to fraction of inspired oxygen (PaO2/FiO2)

The severity of hypoxemia defines the severity of ARDS and associated mortality risk:

▪ Mild (27% mortality risk): PaO2/FiO2>200mmHgbut ≤ 300 mmHg, [positive end-expiratory pressure (PEEP) ≥ 5 cm H2O]

▪ Moderate (32% mortality risk): PaO2/FiO2 >100 mmHg but < 200 mmHg [PEEP ≥ 5 cm H2O]

▪ Severe (45% mortality risk): PaO2/FiO2 <100 mmHg [PEEP ≥5 cm H2O]

Management

Initial therapy should focus on treating the underlying cause of ARDS (i.e antibiotics for infections, reversing antidote for overdoses, etc) and maintaining adequate gas exchange while minimizing complications that are common in patients with ARDS

The following treatment modalities may be used:

Mechanical ventilation lung protective strategy:

¾ Low tidal volume ventilation: In patients with ARDS, positive pressure ventilation may generate extreme pressure in the distal

airways due to the decrease in lung compliance from pulmonary edema, proteinaceous material, and fibrosis This can lead to further lung damage, resulting in worsened hypoxemia, pneumothorax, and pneumomediastinium (coined ventilator induced lung injury and barotrauma) Therefore, the lung protective strategy approach to mechanical ventilation in ARDS patients is to minimize the elevated distal airway pressure (displayed by the mechanical ventilator as the plateau pressure) by utilizing low tidal volumes defined as 6-8 mL/kg of ideal body weight [53] Mortality is also reduced with low distal airway pressures (plateau pressure <30cm H2O) [54,55] Our experience has been to utilize lung protective strategies by targeting tidal volumes to 6-8 mL/

kg of ideal body weight

¾ PEEP: One of the factors that may contribute to ventilator induced lung injury is inflammation from cyclic atelectasis (termed

alectotrauma) PEEP improves oxygenation and prevents alectotrauma, although it is unclear at what level of PEEP prevents this complication [55-57] Several studies have evaluated various approaches to utilizing PEEP with conflicting results [58-62] While some studies report no difference in mortality between higher versus lower levels of PEEP [58], other studies illustrate an improved mortality with higher levels of peep in patients with severe hypoxemia (PaO2/FiO2<200mmHg) [61,62] Furthermore, studies have shown a decrease in hypoxemia, ventilator free days, and days free of organ failure when combined with a low tidal volume strategy [59,60] While nearly all patients should have a minimum PEEP of 5 cm H2O, PEEP is increased to a plateau pressure of 30-32 cm H2O in patients with severe hypoxemia (PaO2/FiO2<200mmHg)

¾ Fluid management strategies: Patients with ARDS have non-cardiogenic pulmonary edema due to vascular permeability from

inflammation and changes in oncotic forces due to damage to the alveolar-capillary interface Conservative fluid management approaches have shown to have a significant clinical benefit by decreasing ventilator free days, ICU days, improved oxygenation and lung injury scores [63] A conservative fluid management strategy should therefore be pursued as long as the patient is not

in shock or experiencing hypo perfusion Effective fluid strategies can be achieved with daily diuretics, avoiding unnecessary intravenous fluids, and meticulously monitoring fluid intake/output and electrolytes if diuretics are utilized

¾ Novel therapies: Several other therapies and management strategies have been utilized in the management of ARDS such as

systemic steroids [64], antioxidants [65] and prone positioning [66] to improve oxygenation The benefits of these treatment modalities remain controversial and should be approached with caution under the direction of a physician that is an expert in the management of patients with ARDS

¾ Supportive care: Appropriate supportive measures should be given to all patients in the ICU Maintaining adequate nutrition,

sedation and pain control is paramount but often overseen The prevention of secondary infections by maintaining aggressive hand hygiene, ventilator-associated infection preventative measures, and diligent central venous and urinary catheter care is vital Gastric ulcers and deep venous thrombosis prophylaxis should be addressed on a case-by-case basis

Conclusion

COPD, asthma and ARDS are common pulmonary disorders encountered in the ICU COPD and asthma are initially managed initially with rapid bronchodilators, anti-inflammatory steroids, and oxygenation via invasive and non-invasive ventilation In patients with ARDS, management focuses primarily on treating the underlying cause, lung protective strategies for those receiving mechanical ventilation, and adequate supportive care Management of all these conditions can be challenging and a consultation by experts in critical care medicine is often warranted Providers caring for critically ill patients should be familiar with the identification and management of patients with COPD, asthma and ARDS

References

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2 http://www.cdc.gov/copd/

3 Mackay AJ, Hurst JR (2013) COPD exacerbations: causes, prevention, and treatment Immunol Allergy Clin North Am 33: 95-115.

4 Stoller JK (2002) Clinical practice Acute exacerbations of chronic obstructive pulmonary disease N Engl J Med 346: 988-994.

5 Vestbo J, Hurd SS, Rodriguez-Roisin R (2012) The 2011 revision of the global strategy for the diagnosis, management and prevention of COPD (GOLD) why and what? Clin Respir J 6: 208-214.

6 Niewoehner DE, Lokhnygina Y, Rice K, Kuschner WG, Sharafkhaneh A, et al (2007) Risk indexes for exacerbations and hospitalizations due to COPD Chest 131: 20-28.

7 Celli BR, MacNee W; ATS/ERS Task Force (2004) Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper Eur Respir J 23: 932-946.

8 Ram FS, Picot J, Lightowler J, Wedzicha JA (2004) Non-invasive positive pressure ventilation for treatment of respiratory failure due to exacerbations

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9 Cydulka RK, Emerman CL (1995) Effects of combined treatment with glycopyrrolate and albuterol in acute exacerbation of chronic obstructive pulmonary disease Ann Emerg Med 25: 470-473.

10 O’Driscoll BR, Taylor RJ, Horsley MG, Chambers DK, Bernstein A (1989) Nebulised salbutamol with and without ipratropium bromide in acute airflow obstruction Lancet 1: 1418-1420.

11 [No authors listed] (1994) In chronic obstructive pulmonary disease, a combination of ipratropium and albuterol is more effective than either agent alone An 85-day multicenter trial COMBIVENT Inhalation Aerosol Study Group Chest 105: 1411-1419.

12 Albert RK, Martin TR, Lewis SW (1980) Controlled clinical trial of methylprednisolone in patients with chronic bronchitis and acute respiratory insufficiency Ann Intern Med 92: 753-758.

13 de Jong YP, Uil SM, Grotjohan HP, Postma DS, Kerstjens HA, et al (2007) Oral or IV prednisolone in the treatment of COPD exacerbations: a randomized, controlled, double-blind study Chest 132: 1741-1747.

14 Sayiner A, Aytemur ZA, Cirit M, Unsal I (2001) Systemic glucocorticoids in severe exacerbations of COPD Chest 119: 726-730.

15 Stanbrook MB, Goldstein RS (2001) Steroids for acute exacerbations of COPD : how long is enough? Chest 119: 675-676.

16 Vollenweider DJ, Jarrett H, Steurer-Stey CA, Garcia-Aymerich J, Puhan MA (2012) Antibiotics for exacerbations of chronic obstructive pulmonary disease Cochrane Database Syst Rev 12: CD010257.

17 Sethi S (2002) Acute Exacerbations of COPD: a “multipronged” approach J Respir Dis 23: 217-225

21 McFadden ER Jr, Warren EL (1997) Observations on asthma mortality Ann Intern Med 127: 142-147.

22 Eisner MD, Lieu TA, Chi F, Capra AM, Mendoza GR, et al (2001) Beta agonists, inhaled steroids, and the risk of intensive care unit admission for asthma Eur Respir J 17: 233-240.

23 Turner MO, Noertjojo K, Vedal S, Bai T, Crump S, et al (1998) Risk factors for near-fatal asthma A case-control study in hospitalized patients with asthma Am J Respir Crit Care Med 157: 1804-1809.

24 Dutta EJ, Li JT (2002) Beta-agonists Med Clin North Am 86: 991-1008.

25 Shim C, Williams MH Jr (1980) Bronchial response to oral versus aerosol metaproterenol in asthma Ann Intern Med 93: 428-431.

26 Salmeron S, Brochard L, Mal H, Tenaillon A, Henry-Amar M, et al (1994) Nebulized versus intravenous albuterol in hypercapnic acute asthma A multicenter, double-blind, randomized study Am J Respir Crit Care Med 149: 1466-1470.

27 Kay AB (1991) Asthma and inflammation J Allergy Clin Immunol 87: 893-910.

28 Idris AH, McDermott MF, Raucci JC, Morrabel A, McGorray S, et al (1993) Emergency department treatment of severe asthma Metered-dose inhaler plus holding chamber is equivalent in effectiveness to nebulizer Chest 103: 665-672.

29 Williams SG, Schmidt DK, Redd SC, Storms W (2003) Key clinical activities for quality asthma care Recommendations of the National Asthma Education and Prevention Program MMWR Recomm Rep 52: 1-8.

30 Rebuck AS, Chapman KR, Abboud R, Pare PD, Kreisman H, et al (1987) Nebulized anticholinergic and sympathomimetic treatment of asthma and chronic obstructive airways disease in the emergency room Am J Med 82: 59-64.

31 Rodrigo GJ, Rodrigo C (2000) First-line therapy for adult patients with acute asthma receiving a multiple-dose protocol of ipratropium bromide plus albuterol in the emergency department Am J Respir Crit Care Med 161: 1862-1868.

32 McFadden ER Jr (2003) Acute severe asthma Am J Respir Crit Care Med 168: 740-759.

33 Skobeloff EM, Spivey WH, McNamara RM, Greenspon L (1989) Intravenous magnesium sulfate for the treatment of acute asthma in the emergency department JAMA 262: 1210-1213.

34 Krishnan V, Diette GB, Rand CS, Bilderback AL, Merriman B, et al (2006) Mortality in patients hospitalized for asthma exacerbations in the United States Am J Respir Crit Care Med 174: 633-638.

35 Soroksky A, Stav D, Shpirer I (2003) A pilot prospective, randomized, placebo-controlled trial of bilevel positive airway pressure in acute asthmatic attack Chest 123: 1018-1025.

36 Fernández MM, Villagrá A, Blanch L, Fernández R (2001) Non-invasive mechanical ventilation in status asthmaticus Intensive Care Med 27: 486-492.

37 Patrick W, Webster K, Ludwig L, Roberts D, Wiebe P, et al (1996) Noninvasive positive-pressure ventilation in acute respiratory distress without prior chronic respiratory failure Am J Respir Crit Care Med 153: 1005-1011.

38 Meduri GU, Cook TR, Turner RE, Cohen M, Leeper KV (1996) Noninvasive positive pressure ventilation in status asthmaticus Chest 110: 767-774.

39 Shivaram U, Miro AM, Cash ME, Finch PJ, Heurich AE, et al (1993) Cardiopulmonary responses to continuous positive airway pressure in acute asthma J Crit Care 8: 87-92.

40 Brenner B, Corbridge T, Kazzi A (2009) Intubation and mechanical ventilation of the asthmatic patient in respiratory failure J Allergy Clin Immunol 124: 19-28

41 Gluck EH, Onorato DJ, Castriotta R (1990) Helium-oxygen mixtures in intubated patients with status asthmaticus and respiratory acidosis Chest 98: 693-698.

42 Manthous CA, Hall JB, Caputo MA, Walter J, Klocksieben JM, et al (1995) Heliox improves pulsus paradoxus and peak expiratory flow in nonintubated patients with severe asthma Am J Respir Crit Care Med 151: 310-314.

43 Kress JP, Noth I, Gehlbach BK, Barman N, Pohlman AS, et al (2002) The utility of albuterol nebulized with heliox during acute asthma exacerbations

Am J Respir Crit Care Med 165: 1317-1321.

44 Schaeffer EM, Pohlman A, Morgan S, Hall JB (1999) Oxygenation in status asthmaticus improves during ventilation with helium-oxygen Crit Care Med 27: 2666-2670.

45 Saulnier FF, Durocher AV, Deturck RA, Lefèbvre MC, Wattel FE (1990) Respiratory and hemodynamic effects of halothane in status asthmaticus Intensive Care Med 16: 104-107.

46 Johnston RG, Noseworthy TW, Friesen EG, Yule HA, Shustack A (1990) Isoflurane therapy for status asthmaticus in children and adults Chest 97: 698-701.

47 Hemming A, MacKenzie I, Finfer S (1994) Response to ketamine in status asthmaticus resistant to maximal medical treatment Thorax 49: 90-91.

48 Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, et al (2005) Incidence and outcomes of acute lung injury N Engl J Med 353: 1685-1693.

49 Dantzker DR, Brook CJ, Dehart P, Lynch JP, Weg JG (1979) Ventilation-perfusion distributions in the adult respiratory distress syndrome Am Rev Respir Dis 120: 1039-1052.

50 Roupie E, Dambrosio M, Servillo G, Mentec H, el Atrous S, et al (1995) Titration of tidal volume and induced hypercapnia in acute respiratory distress syndrome Am J Respir Crit Care Med 152: 121-128.

51 Villar J, Blazquez MA, Lubillo S, Quintana J, Manzano JL (1989) Pulmonary hypertension in acute respiratory failure Crit Care Med 17: 523-526.

52 Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, et al (2012) Acute respiratory distress syndrome: the Berlin Definition JAMA 307: 2533.

2526-53 Sud S, Sud M, Friedrich JO, Wunsch H, Meade MO, et al (2013) High-frequency ventilation versus conventional ventilation for treatment of acute lung injury and acute respiratory distress syndrome Cochrane Database Syst Rev 2:CD004085

54 [No authors listed] (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome The Acute Respiratory Distress Syndrome Network N Engl J Med 342: 1301-1308.

55 Needham DM, Colantuoni E, Mendez-Tellez PA, Dinglas VD, Sevransky JE, et al (2012) Lung protective mechanical ventilation and two year survival

in patients with acute lung injury: prospective cohort study BMJ 344: e2124.

56 Webb HH, Tierney DF (1974) Experimental pulmonary edema due to intermittent positive pressure ventilation with high inflation pressures Protection

by positive end-expiratory pressure Am Rev Respir Dis 110: 556-565.

57 Muscedere JG, Mullen JB, Gan K, Slutsky AS (1994) Tidal ventilation at low airway pressures can augment lung injury Am J Respir Crit Care Med 149: 1327-1334.

58 Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, et al (2004) Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome N Engl J Med 351: 327-336.

59 Meade MO, Cook DJ, Guyatt GH, Slutsky AS, Arabi YM, et al (2008) Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial JAMA 299: 637-645.

60 Mercat A, Richard JC, Vielle B, Jaber S, Osman D, et al (2008) Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial JAMA 299: 646-655.

61 Briel M, Meade M, Mercat A, Brower RG, Talmor D, et al (2010) Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis JAMA 303: 865-873.

62 Gattinoni L, Caironi P (2008) Refining ventilatory treatment for acute lung injury and acute respiratory distress syndrome JAMA 299: 691-693.

63 National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Wiedemann HP, Wheeler AP, et al (2006) Comparison of two fluid-management strategies in acute lung injury N Engl J Med 354: 2564-2575.

64 Steinberg KP, Hudson LD, Goodman RB, Hough CL, Lanken PN, et al (2006) Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome N Engl J Med 354: 1671-1684.

65 Gadek JE, DeMichele SJ, Karlstad MD, Pacht ER, Donahoe M, et al (1999) Effect of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome Enteral Nutrition in ARDS Study Group Crit Care Med 27: 1409-1420.

66 Sud S, Friedrich JO, Taccone P, Polli F, Adhikari NK, et al (2010) Prone ventilation reduces mortality in patients with acute respiratory failure and severe hypoxemia: systematic review and meta-analysis Intensive Care Med 36: 585-599.

Bedside approach to Gastrointestinal

Bleeding in the Intensive Care Unit

Disclosure/Funding: Dr Ramzy Rimawi is on the speakers’ bureau for ALK-Abello None of the other authors have conflicts of interest None of the authors have received funding for this manuscript

Keywords: Bleeding; Critical care; Gastrointestinal system; Intensive care; Resuscitation

Introduction

Acute gastrointestinal bleeding is a common problem in the intensive care unit (ICU) Depending on comorbidities and other critical factors, it can be potentially life threatening and thus, requires prompt assessment and often multidisciplinary medical management [1] Admission to ICU takes into account various “high-risk” profiles, which are often associated with a poor outcome and prolonged ICU stay [2,3] These features include hemodynamic instability, incessant bleeding, coagulopathy, aspirin use, comorbid conditions and age above 65 years, anemia, elevated blood urea nitrogen and leukocytosis [3] This chapter will integrate current research findings and recommendations for managing ICU adult patients with GI bleeding

Although the BLEED classification tool developed in 1997 suggested a great percentage of low-risk patients were hospitalized in the ICU, it helped to identify high-risk patients that required immediate intervention, developed bleed recurrence, required surgery for source control, and had increased mortality [4] High-risk patients had additional multi-organ failure, required more transfusions of blood products, and were hospitalized for longer periods of time The BLEED criteria should be used as a triage prediction tool for of ICU admission, as well as probable length of stay in the hospital Other prognostic indicators include the Rockall bleeding score and the Glasgow Blachford prognostic scales

Upper vs Lower GIB

Gastrointestinal (GI) bleeding can be overt (i.e., hematemesis, coffee-ground emesis, hematochezia, melena) or occult Occult blood can be detected by guaiac examination of the stool Acute upper GI bleed (AUGIB) has a yearly incidence of 40-150 per 100,000 persons, with a 6-10% mortality rate [5] Acute lower GI bleed (ALGIB) is defined as bleeding distal to the ligament of Treitz and has incidence estimated at 20-30 per 100,000 adults ALGIB is primarily caused by non-life threatening anal pathology, with hemorrhoids or fissures being the most common cause of rectal bleeding in individuals up to 30 years of age In older individuals, the main source is colonic diverticula (80%)

Overall, 80% of GI bleeds cease without intervention However, the overall risk of recurrence is about 25% Moreover, the mortality rate increases in patients with advanced age and comorbid conditions, specifically renal and/or hepatic dysfunction, heart disease, and malignancy Intermittent or spontaneous cessation of bleeding, along with anatomical barriers such as the intra-peritoneal location of the intestines, the robust intestinal contractility, and the superimposed bowel loops lead to an overall difficulty of diagnosing a precise source for ALGIB in 10% of the cases [6] (Table 1) The Rockall Scoring System is a parameter used for stratifying the risks of rebleeding and death after admission to the hospital for an acute GI bleed

Ulcers (esophageal, gastric, duodenal) Diverticulosis Dieulafoy’s lesions Ischemic colitis Arterial-venous malformations Vascular ectasias Varices (esophageal, gastric) Hemorrhoids Aortoesophageal fistula Rectal varices

NSAID induced Inflammatory Bowel Disease

Table 1: Causes of AUGIB and ALGIB.

Risk Factors

Medications

There are various reversible and irreversible pharmacologic agents associated with GI bleeding For example, numerous studies have illustrated the risk of GI bleed and GI perforation with non-steroidal anti-inflammatory drugs (NSAID) use [7] As the incidence of GI bleeding in elderly patients using NSAIDS is up to 1 in 7 persons, NSAID use is responsible for about 30% of GI bleed hospitalizations and mortality [8] Multiple locations, including gastric, duodenal and pre-pyloric areas may be affected by NSAID use Aspirin is

Diana A Gliga, Ramzy H Rimawi, Zahid Vahora and Mark

A Mazer

Brody School of Medicine at East Carolina University, Jacksonville, NC

28546, USA

*Corresponding author: Diana A Gliga, MS, Brody School of

Medicine at East Carolina University, 134 Empire BLVD, Jacksonville,

associated with about a 4-time increase risk of GI bleed Coating the ASA enterically does not reduce its’ risk There is also a positive correlation between higher doses of ASA and GI bleed The concomitant use of clopidogrel and warfarin versus monotherapy is related

to higher incidence of bleeding

Comorbidities

Age over 65 years is the strongest risk factor GI bleeding and is associated with increased morbidity and mortality compared with the general population [7,9] Male gender, extensive comorbidities, prior history of complicated peptic ulcer disease or alcoholic cirrhosis, and presence of neoplasm are other common risk factors associated with poor prognosis Rebleeding is primarily encountered in hemodynamically unstable patients or those with elevated blood urea nitrogen, creatinine, or liver enzymes (particularly aminotransferases) Other risks for rebleeding include GI hemorrhage (>20 g/L reduction in hemoglobin), septic shock, prior abdominal aortic aneurysm repair, and malnutrition [10] As expected, length of stay in the ICU is prolonged in these patients The incidence of stress associated GI bleed is about 0.17% due to the use of routine prophylaxis in the ICU

Esophageal or gastric variceal bleeding is associated with portal hypertension, the most common cause of morbidity and mortality

in liver cirrhosis [12] When the hepatic venous pressure exceeds 12 mmHg, acute esophageal variceal bleeding can occur With an associated mortality rate of 20-25%, clinical scoring predicting the risk of bleeding in this patient population is of tremendous importance Cholinesterase level <2.25 kU/L, INR >1.2, variceal presence and viral or alcoholic etiology were four parameters effective in identifying high-risk patients [13] These factors were used to supplement EGD diagnostic power Treating the underlying cause is an essential part

of variceal bleeding prevention This includes hepatitis C antiviral therapy, alcohol abstinence, and iron chelation Other modalities that may prevent rebleeding secondary to portal hypertension include nitrates, non-selective beta-blockers, and diuretics [12] The efficacy of the somatostatin analogue, octreotide, in stopping variceal bleeding is controversial [14]

Dysenteric diarrhea

Infectious diarrhea involving dysentery can be caused by enteric pathogens such as Salmonella, Shigella, enterohemorrhagic E coli (O157:H7), enteroinvasive E coli, Yersinia, Entamoeba histolytica, and Clostridium difficile Campylobacter jejuni is the most common

identified organism, associated with grossly blood diarrhea in up to 91% of patients [15] Stool cultures are usually requested but their yield

is low (0.9% in Salmonella, 0.6% in Shigella, 1.4% in Campylobacter, and 0.3% in E coli O157 infections) Presence of stool leukocytes and

fecal lactoferrin are also used in guiding infectious etiology of bloody stools The “three day rule” is enforced to diminish extraneous stool

cultures in patients with non-Clostridium difficile diarrhea related to hospitalization >3 days Exceptions to this include HIV, neutropenia, age over 65 years, or those with questionable C difficile infection.

Diverticular disease

Diverticular bleeding accounts for approximately 40% of ALGIB [16] As diverticulosis incidence increases with age, diverticular bleeding is an important consideration in the differential diagnosis of GI bleeding They can often present without pain, potentially making the presentation of such a patient misleading Such bleeds can be arterial in origin, frequently from the neck or dome of the diverticulum [17] While diverticular bleeds often cease without intervention, they have high rates of rebleeding, often prompting further radiologic studies as there is a wide range in diagnostic yield of colonoscopy in all ALGIB, ranging from 48-90% [18]

Resuscitation

Aggressive hemodynamic resuscitation is imperative in patients with rapid bleeding, defined as a hemorrhage >100 mL/hr with signs of hypovolemic shock (i.e., tachycardia, hypotension, tachypnea) The estimated blood volume depletion in such cases is 15% Hemodynamic stability is a provider’s top priority and should supersede diagnostic interventions [19]

Setup and consult requisitions

Aggressive and early resuscitation in the ICU care is warranted in patients who meet high-risk criteria with hemodynamic instability, active hemorrhage, and/or comorbid risk factors Immediate intravenous access should be obtained with large bore peripheral catheters

or a central venous line Large bore venous access, ideally through peripheral catheters, is essential for volume resuscitation, serial blood count monitoring, medication infusion(s), and transfusion of blood products when appropriate Consultation with gastroenterology, general surgery, and/or interventional radiology should be requested early to avoid delays in diagnostic and therapeutic interventions

Hemostasis control

Most AUGIB secondary to peptic ulcers and other non-variceal bleeds cease spontaneously [15] However, the majority of patients with bleeding, and rebleeding complications require hemostasis with the use of endoscopic therapy to obtain source control Despite rapid endoscopic repair, subsequent rebleeding occurs in 20% of patients Histamine-2-receptor antagonists are efficient in preventing these rebleeding episodes; however, their use is limited in reducing the need for transfusions or surgical interventions While intravenous proton pump inhibitors (PPI) are effective in reducing bleeding recurrences, they have little-to-no impact on mortality or need for surgery [20-22]

cognitive impairment may become clinically apparent In cases of acute GI bleeding at hemoglobin levels below 7-8 g/dL, the risk of postoperative death increases Based on randomized trials, hemoglobin goals in the ICU are a concentration of 7 g/dL in hemodynamically stable young patients without comorbidities and 8 g/dL for other medical or surgical patients who are hemodynamically stable [23] A liberal transfusion trigger of hemoglobin level of 10 g/dL was associated with higher mortality than a restrictive trigger of 7 g/dl, except

in older patients and those with active coronary artery disease [24] If the patient is hemodynamic stable, esophagogastroduodenoscopy (EGD) can be performed during the blood product transfusion [25] If coagulopathy is present, fresh frozen plasma (FFP), prothrombin complex concentrate, or cryoprecipitate should be transfused depending on the circumstances As FFP (typically dosed 10-15 mL/kg) contains about 70% of the original coagulant factor VIII, normal stable clotting factor levels, albumin and immunoglobulins, is not recommended when INR is below <1.5 [26] Platelet infusions are recommended when platelet counts fall below 50,000/microL [3]

Anticoagulation

The incidence of acute GI bleeding from oral anticoagulants (OA) is higher than the incidence related to acetaminophen, NSAIDs, and aspirin (ASA) [4] Dabigatran is particularly problematic in patients with superimposed renal failure [27] Concomitant anticoagulants and/or antiplatelet therapies yield a greater risk of GI bleeding: 8.0 incidence ratio (IR) versus OA use with Tylenol (4.4 IR) and OA use with ASA (3.8 IR) [4] If the risks of anticoagulants and platelet inhibitor agents outweigh their benefits, these agents, including aspirin, should be held in patients with GI bleeding [4] While there are no set criteria for these scenarios, consulting the prescribing provider in

a timely fashion is highly recommended [3] Reversal of these agents is often necessary to help achieve timely source control In patients with INR is >3, EGD may need to be postponed until the anticoagulation is reversed If the INR is still >1.5 prior to the procedure, fresh frozen plasma can also be administered during the endoscopy

Additional pharmacologic modalities for GI hemorrhage management are under investigation In animal models, nitric oxide-based therapy (i.e., nitroglycerin) helps reduce the NSAID induced damage to the gastric mucosa However, this effect may be limited by an inhibitory effect on platelet aggregation [8] Statistical analysis of agents that predispose to a bleeding event showed an odds-ratio (OR) of 7.4 with NSAIDS, 2.4 with aspirin, and 0.6 with nitro-vasodilators and anti-secretory therapies [28]

Diagnosis/Management

The diagnostic tool of choice in patients who have been resuscitated is colonoscopy and esophagogastroduodenoscopy (EGD) for ALGIB and AUGIB, respectively

AUGIB pre-endoscopic management

An appropriate history and physical can help direct one’s clinical suspicion as to the cause of a patient’s bleeding The suspicion of peptic ulcer disease will prompt a clinician to infuse a PPI (80mg bolus, followed by 8mg/hr) versus a history of liver cirrhosis, which would prompt octreotide infusion [14,29] Unfortunately in the ICU setting, appropriate history acquisition can be difficult and clinical judgment must often be used

Active bleeding, a visible vessel at the ulcer base with an adherent clot, and an ulcer larger than 2 cm are factors associated with a greater risk of re-bleeding [9] In these patients, endoscopic interventions such as cautery, injection, or hemoclipping therapies are effective

in achieving hemostasis during acute bleeding and may help decrease the risk of future bleeding Early EGD can improve outcome while reducing ICU length of stay and rate of re-bleed [30] Conversely, inaccurate diagnosis due to delayed endoscopy increases risks of re-bleed, surgery, hospitalization, ICU stay, and ICU re-admission In patients without frank signs of AUGIB, a lavage via nasogastric tube may be done to help identify whether the bleeding is distal to ligament of Treitz EGD should follow a bloody lavage [5] However, nasogastric lavage remains controversial as approximately 15% of gastric aspirates in patients with AUGIB will not yield blood return [31] Radionuclide imaging and computed tomographic (CT) angiography are two other useful diagnostic interventions However, their sensitivity depends on the presence of active bleeding during the examination Post-procedure high-dose PPI infusion is recommended for 72 hours to reduce the risk of rebleeding in patients with ulcers and high risk stigmata [14]

ALGIB pre-endoscopic management

Colonoscopy can diagnose the source of up to 89% of ALGIB, as compared to angiography, which has a diagnostic sensitivity of about 41% [5] Colonoscopy can provide for direct visualization of the entire colon, biopsy, and therapy (laser, pharmaceutical, or physical ligation) Colonoscopy is associated with low mortality and morbidity risks (0.1% and 0.3% respectively) and shortened length of stay [14] Urgent colonoscopy can result in successful permanent hemostasis in 67% of the cases [32]

Specialized procedures are employed in cases where the source of bleeding is more enigmatic These include Meckel’s scan, barium contrast upper GI series with small bowel follow-through, technetium-99m–tagged red blood cell scan, and push enteroscopy [5] Nuclear studies (i.e., technetium-99m–tagged red blood cell scan) are indicated in cases with a low rate of bleeding (0.1 to 0.4 mL per minute) The accuracy is increased when used concomitantly with arteriography Angiography is the desired diagnostic tool if the rate of bleeding

is approximately 0.5 mL/min, and if the patient experiences active bleeding However, this intervention is invasive and nephrotoxic Sensitivity is also poorer than that of colonoscopies, with an estimated upper range of 65% [19] The advantages include embolization and infusion of vasoactive treatment

Push enteroscopy or endoscopy is a procedure reserved for identifying small bowel bleeding past the ligament of Treitz (2-10% of all

GI bleeding cases) [5] This procedure is essentially an upper endoscopy with an additional 15-160 cm of small intestine visualization The evaluator can take biopsy samples and apply treatment, but the diagnostic yield reaches a mere 54% While capsule endoscopy is painless, non-invasive and has a diagnostic yield of 66-69%, biopsies cannot be taken As a last resort, exploratory laparotomy may be employed, with a sensitivity of 70% in locating GI bleeding sources [5]

While sclerotherapy and variceal band ligation with rubber rings via endoscopy can help control or prevent rebleeding in patients who cannot tolerate beta blockade, it does not reduce the portal pressure In cirrhotic patients, variceal bleeding related to portal hypertension can be managed via transjugular intrahepatic portosystemic shunting (TIPS) If placed within three days, TIPS improved two-year survival, reduced rebleeding rates, and reduced the risk of hepatic encephalopathy Given the risk of esophageal rupture, balloon tamponade is only reserved for 24-hour hemostasis in patients with massive bleeding In cirrhotic patients, the only definitive therapy for variceal rebleeding is liver transplantation [12]

Stress Ulcers Prophylaxis

Ulceration and stress-related mucosal disease (SRMD) are some of the more common GI complications in patients hospitalized in the ICU, with an associated increase mortality rate [33] The majority of critically ill patients who develop SRMD are affected within 24 hours of admission to ICU, likely related to acid production and ischemia Suppressing hydrogen ion production with antacids, sucralfate, histamine2-receptor antagonists or PPI is critical in SRMD prophylaxis [13] Ranitidine and enteral feeding were shown to be superior

to sucralfate in ensuring lower bleeding rates in mechanically ventilated patients [34] While a gastric pH >4 is adequate to prevent stress ulcers, a pH >6 is necessary to prevent rebleeding from a peptic ulcer Also, while both IV histamine-2-receptor antagonists and PPIs increase the gastric pH, maintenance at pH >6 are primarily achieved with PPIs [22] As critically ill patients rarely develop clinically significant GI bleeding, stress ulcer prophylaxis should be withheld unless they have a coagulopathy or require mechanical ventilation [34]

Other Considerations

Restarting aspirin for primary cardiovascular prophylaxis is not recommended, except in secondary prophylaxis for patients with a history of CAD where it is recommended to restart soon (1-7 days) in addition to a PPI In terms of restarting NSAIDs in patients with bleeding ulcers, it is recommended not to resume NSAIDs and, if necessary, cyclo-oxygenase (Cox)-2 selective NSAIDS be started with PPI [38]

Conclusion

The ICU provider plays an important role in coordinating and managing the care of high-risk patients with acute GI bleeding These patients require intensive clinical and hemodynamic monitoring, correction of coagulopathy, appropriate pharmacologic intervention, and rapid diagnostic and therapeutic intervention As GI bleeds are frequently encountered in the ICU setting, ICU providers should obtain adequate education and training in the timely and effective management of acute GI bleeds

3 Strate L (2013) Approach to resuscitation and diagnosis of acute lower gastrointestinal bleeding in the adult patient UpToDate

4 Kollef MH, O’Brien JD, Zuckerman GR, Shannon W (1997) BLEED: a classification tool to predict outcomes in patients with acute upper and lower gastrointestinal hemorrhage Crit Care Med 25: 1125-1132

5 Manning-Dimmitt LL, Dimmitt SG, Wilson GR (2005) Diagnosis of gastrointestinal bleeding in adults Am Fam Physician 71: 1339-1346

6 Imdahl A (2001) Genesis and pathophysiology of lower gastrointestinal bleeding Langenbecks Arch Surg 386: 1-7

7 Gutthann SP, García Rodríguez LA, Raiford DS (1997) Individual nonsteroidal antiinflammatory drugs and other risk factors for upper gastrointestinal bleeding and perforation Epidemiology 8: 18-24

8 Bhatt DL, Scheiman J, Abraham NS, Antman EM, Chan FK, et al (2008) ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents J Am Coll Cardiol 52: 1502-1517

9 Pitchumoni CS, Brun A (2012) Geriatric Gastroenterology Springer, New York

10 Pimentel M, Roberts DE, Bernstein CN, Hoppensack M, Duerksen DR (2000) Clinically significant gastrointestinal bleeding in critically ill patients in an era of prophylaxis Am J Gastroenterol 95: 2801-2806

11 Ellison RT, Perez-Perez G, Welsh CH, Blaser MJ, Riester KA, et al (1996) Risk factors for upper gastrointestinal bleeding in intensive care unit patients: role of helicobacter pylori Federal Hyperimmune Immunoglobulin Therapy Study Group Crit Care Med 24: 1974-1981

12 Ashkenazi E, Kovalev Y, Zuckerman E (2013) Evaluation and treatment of esophageal varices in the cirrhotic patient Isr Med Assoc J 15: 109-115

13 Tacke F, Fiedler K, Trautwein C (2007) A simple clinical score predicts high risk for upper gastrointestinal hemorrhages from varices in patients with chronic liver disease Scand J Gastroenterol 42: 374-382

14 Hwang JH, Fisher DA, Ben-Menachem T, Chandrasekhara V, Chathadi K, et al (2012) The role of endoscopy in the management of acute variceal upper GI bleeding Gastrointest Endosc 75: 1132-1138

non-15 Guerrant RL, Van Gilder T, Steiner TS, Thielman NM, Slutsker L, et al (2001) Practice guidelines for the management of infectious diarrhea Clin Infect Dis 32: 331-351

16 Schuetz A, Jauch KW (2001) Lower gastrointestinal bleeding: therapeutic strategies, surgical techniques and results Langenbecks Arch Surg 386: 17-25

17 Davila RE, Rajan E, Adler DG, Egan J, Hirota WK, et al (2005) ASGE Guideline: the role of endoscopy in the patient with lower-GI bleeding Gastrointest Endosc 62: 656-660

18 Zuckerman GR, Prakash C (1998) Acute lower intestinal bleeding: part I: clinical presentation and diagnosis Gastrointest Endosc 48: 606-617

19 Edelman DA, Sugawa C (2007) Lower gastrointestinal bleeding: a review Surg Endosc 21: 514-520

20 Conrad SA (2002) Acute upper gastrointestinal bleeding in critically ill patients: causes and treatment modalities Crit Care Med 30: S365-368

21 Cochran EB, Phelps SJ, Tolley EA, Stidham GL (1992) Prevalence of, and risk factors for, upper gastrointestinal tract bleeding in critically ill pediatric patients Crit Care Med 20: 1519-1523

22 Carson J, Kleinman S (2013) Indications and hemoglobin thresholds for red blood cell transfusion in the adult UpToDate.

23 Hébert PC, Wells G, Blajchman MA, Marshall J, Martin C, et al (1999) A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group N Engl J Med 340: 409-417

24 Villanueva C, Colomo A, Bosch A, Concepción M, Hernandez-Gea V, et al (2013) Tranfusion strategies for acute upper gastrointestinal bleeding N Engl J Med 368: 11-21

25 Wychowski MK, Kouides PA (2012) Dabigatran-induced gastrointestinal bleeding in an elderly patient with moderate renal impairment Ann Pharmacother 46: e10

26 Liumbruno G, Bennardello F, Lattanzio A, Piccoli P, Rossetti G; Italian Society of Transfusion Medicine and Immunohaematology (SIMTI) Work Group (2009) Recommendations for the transfusion of plasma and platelets Blood Transfus 7: 132-150

27 Lanas A, Bajador E, Serrano P, Fuentes J, Carreño S, et al (2000) Nitrovasodilators, low-dose aspirin, other nonsteroidal antiinflammatory drugs, and the risk of upper gastrointestinal bleeding N Engl J Med 343: 834-839

28 Chak A, Cooper GS, Lloyd LE, Kolz CS, Barnhart BA, et al (2001) Effectiveness of endoscopy in patients admitted to the intensive care unit with upper

GI hemorrhage Gastrointest Endosc 53: 6-13

29 Corley DA, Cello JP, Adkisson W, Ko WF, Kerlikowske K (2001) Octreotide for acute esophageal variceal bleeding: a meta-analysis Gastroenterology 120: 946-954

30 Ohyama T, Sakurai Y, Ito M, Daito K, Sezai S, et al (2000) Analysis of urgent colonoscopy for lower gastrointestinal tract bleeding Digestion 61: 189-192

31 Cuellar RE, Gavaler JS, Alexander JA, Brouillette DE, Chien MC, et al (1990) Gastrointestinal tract hemorrhage The value of a nasogastric aspirate Arch Intern Med 150: 1381-1384

32 Stollman N, Metz DC (2005) Pathophysiology and prophylaxis of stress ulcer in intensive care unit patients J Crit Care 20: 35-45

33 Fennerty MB (2002) Pathophysiology of the upper gastrointestinal tract in the critically ill patient: rationale for the therapeutic benefits of acid suppression Crit Care Med 30: S351-355

34 Cook D, Heyland D, Griffith L, Cook R, Marshall J, et al (1999) Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation Canadian Critical Care Trials Group Crit Care Med 27: 2812-2817

35 Baradarian R, Ramdhaney S, Chapalamadugu R, Skoczylas L, Wang K, et al (2004) Early intensive resuscitation of patients with upper gastrointestinal bleeding decreases mortality Am J Gastroenterol 99: 619-622

36 Shorr AF, Trotta RF, Alkins SA, Hanzel GS, Diehl LF (1999) D-dimer assay predicts mortality in critically ill patients without disseminated intravascular coagulation or venous thromboembolic disease Intensive Care Med 25: 207-210

37 Kapsoritakis AN, Koukourakis MI, Sfiridaki A, Potamianos SP, Kosmadaki MG, et al (2001) Mean platelet volume: a useful marker of inflammatory bowel disease activity Am J Gastroenterol 96: 776-781

38 Laine L, Jensen DM (2012) Management of patients with ulcer bleeding Am J Gastroenterol 107: 345-360.

Renal Disorders in the ICU

Introduction

Acute Kidney Injury (AKI) is a sudden decrease in kidney function due to a reduction in glomerular filtration rate (GFR), increase in creatinine or a decrease in urine output AKI consists of different etiologies including pre-renal, acute tubular necrosis, interstitial nephritis, glomerular and vasculitic renal diseases, and post-renal obstructive nephropathy [1] AKI is commonly seen in critically ill patients with important consequences including increased risk of death even in mild and/or reversible AKI [1]

Acute Kidney Injury

Whether the disorder is pre-renal, intrinsic or post-renal, identifying the underlying etiology is imperative in an intensive care unit (ICU) setting The investigation includes a detailed history, medication reconciliation, assessment for recent exposure to toxins

or trauma, and a detailed review of symptoms

A detailed physical exam should include a careful assessment of patients’ volume status Hypotensive patients are at risk for over-resuscitation after they achieve hemodynamic stability due to a lack of serial fluid status reassessments Fluid overload may present as peripheral edema, jugular venous distention, and/or crackles on lung auscultation Evidence of systemic syndromes or vasculitis may be suggested by a rash, arthritis and signs of embolic events Abdominal distention can direct towards bladder outlet obstruction, ascites, or abdominal compartment syndrome [2]

Laboratory and radiologic tests are key diagnostic modalities in renal disease, regardless of the hospital setting Providers should inquire prior records for baseline renal functions A basic metabolic profile is crucial as the rate of rise of serum creatinine can be suggestive of the underlying etiology; a slow rise is mostly seen with pre-renal etiology whereas in ATN serum creatinine tends to rise at a rate of 0.3-0.5 mg/dL per day A sudden oliguria (urine output <500 mL/day) can also be suggestive of an acute process Urinalysis and microscopy for urine sediment, quantification of urine protein or albumin and fractional excretion of sodium can

be important diagnostic tests that aid in the diagnosis of the underlying origin A renal ultrasound with Doppler can demonstrate obstructive pathologies or anomalies in renal size or structure A renal biopsy is often last resort if the non-invasive evaluation is not sufficient for diagnosis [3]

It is essential to identify patients that are at higher risk of developing AKI as this will allow for certain protective and/or preventative measures to be undertaken [4] High risk individuals and/or susceptibility factors include: dehydration, hypoalbuminemia, advanced age, exposure to nephrotoxic agents, female gender, history of chronic kidney disease (CKD), history of Diabetes Mellitus, history of Heart disease, patients undergoing cardiac surgery, patients with liver disease or malignancy and patients on mechanical ventilation [4,5]

Etiologies of Acute Kidney Injury

Pre-renal acute kidney injury

Pre-renal disorders are responsible for 30-40% of acute renal injury the ICU [6] Pre-renal diseases result from a decreased arterial blood volume or from any process that reduces renal blood/oxygen delivery [3] In pre-renal diseases, the decrease in GFR is

a physiological response to hypoperfusion rather than tissue damage [2]

In the ICU, certain measurements such as a low central venous pressure (CVP) of 1-2 mm Hg or 10-12 mm Hg in ventilator dependent patients may suggest hypovolemia In ventilator dependent patients, a decrease in blood pressure shortly after lung inflation can be used as evidence of inadequate cardiac filling Central venous oxyhemoglobin saturation (ScvO2) below 50% suggests

a low cardiac output If anemia is not the cause of reduced tissue perfusion, a ScvO2 below 25-30% is highly indicative of low cardiac output [6] Pre-renal disease is seen in multiple scenarios:

-Hypovolemic states (i.e acute hemorrhage, diarrhea, or insensible losses) [3]

- Hypervolemic states with low arterial blood volume (i.e acutely decompensated heart failure)[3]

- Acutely decompensated liver disease with portal hypertension [6]

- Alteration in renal vasculature auto-regulation due to non-steroidal anti-inflammatory drugs (NSAIDS) or iodinated contrast [3]

- Rise in intraabdominal pressure >20 mm Hg leading to abdominal compartment syndrome [2]

In the setting of renal hypoperfusion, sodium reabsorption increases and urinary sodium excretion decreases A urine sodium

<20 mEq/L usually indicates a prerenal condition [2] However urine sodium >40 mEq/L does not rule out pre-renal disease [6] Fractional excretion of sodium (FENa) is the most sensitive index for pre-renal disease for patients not exposed to loop diuretics For patients taking diuretics, the fractional excretion of urea (FEUrea) is superior, with a specificity and sensitivity above 95% FEUrea<35% suggests renal hypoperfusion Rapid reversal of renal hypoperfusion is critical, as prolonged ischemia can lead to renal tubular necrosis [2]

NRuba Sarsour 1 * and Tejas Desai 2

1 East Carolina University – Brody School of Medicine, Department of Internal Medicine, Greenville, NC 27834, USA

2 Assistant Professor of Medicine, East Carolina University – Brody School of Medicine, Department of Internal Medicine, Greenville, NC 27834, USA

*Corresponding author: Ruba Sarsour, DO, East Carolina University –

Brody School of Medicine, Department of Internal Medicine, Greenville,

a consequence of acute heart failure Type 5 is AKI and/or acute heart failure that occurs secondary to a systemic disorder like sepsis [8]

In decompensated heart failure, renal injury can be secondary to decreased cardiac output, increased renal venous pressure or activation

of Renin-angiotensin-aldosterone system which leads to systemic vasoconstriction to ensure brain and heart perfusion while decreasing renal perfusion [9]

Acute tubular necrosis

Acute Tubular Necrosis (ATN) is the cause of 50% of cases of acute kidney injury in intensive care unit Unlike pre-renal disease, in ATN, there is parenchymal damage with sloughing of damaged cells into the renal tubules These cells create an obstruction that lead to

an increased pressure in the proximal tubules and a decrease in the glomerular filtration rate With urine microscopy, tubular epithelial cells with epithelial cell casts are pathognomonic of ATN Renal recovery can be expected in >90% of patients who previously had normal baseline function [6] if managed appropriately There are several phases of ATN:

1 Initiation Phase: oxidative injury secondary to prolonged ischemia [5]

2 Extension phase: inflammatory state secondary to initiation phase leading to medullary congestion and hypoxic injury [5]

3 Maintenance phase: restoration of tubule cells [5] It can be either oliguric or nonoliguric Nonoliguric ATN has a better outcome; however, attempts to change from oliguric to non-oliguric have not shown improved outcomes [5]

4 Repair phase: restoration of polarity and function [5]

There are several etiologies that predispose patients to ATN Common causes include:

• Ischemia from prolonged pre-renal state [11]

• Aminoglycosides can cause ATN in 25% of hospitalized patients receiving therapeutic drug levels It is more common in patients with higher risks for AKI It causes a reversible non-oliguric renal injury 5-10 days into treatment Aminoglycosides can remain in renal tissue for up to a month, thus renal function is not restored immediately after discontinuing the drug Streptomycin is the least nephrotoxic of the aminoglycosides Prior to starting an aminoglycoside, experts advocate inquiring into any family history of drug-induced vestibular disorders as well as informed consent that they are aware of the potential nephrotoxicity [11]

• Amphotericin B can have a cumulative nephrotoxic effect Toxicity leads to a type-I renal tubular acidosis Liposomal preparations have lower propensity for nephrotoxicity [2]

• Cyclosporine toxicity is dose dependent and can lead to a type-4 renal tubular acidosis from severe vasoconstriction Blood level monitoring is crucial In some cases, a renal biopsy is needed to distinguish transplant rejection from cyclosporine toxicity Renal function usually improves after reducing the dose or stopping the drug [11]

• Acyclovir can potentiate renal disease Discontinuation of acyclovir usually reverses renal injury [11]

• Cisplatin toxicity is dose-depending and cumulative but can be avoided by hydration prior to the initiation of therapy [11]

• Ethylene Glycol/Methanol poisoning can elevate the osmolar gap and cause an anion gap metabolic acidosis Urine sediment is usually positive for envelope shaped oxalate crystals [2] Toxicity may be managed with fomepizole antidote but hemodialysis

is indicated for refractory metabolic acidosis/AKI [2]

• Rhabdomyolysis can have several etiologies: trauma (crush injury), infection, immobility, drugs (especially statins), electrolyte abnormalities (hypophosphatemia, hypokalemia), snake venom, and status epilepticus [6] Dehydration and acidosis can predispose to the development of myoglobin, which can cause direct tubular damage [11] Rhabdomyolysis of clinical importance commonly occurs with serum creatinine kinase above 20,000-50,000 international units/L [2]

• Hemoglobinuria results from substantial intravascular hemolytic processes due to transfusion reactions or hemolytic anemia [11] Patients would present with elevated lactate dehydrogenase, decreased haptoglobin, and elevated unconjugated bilirubin [2]

• Cast nephropathy is composed of light chains (myeloma) that can lead to direct tubular injury and intratubular obstruction [2]

• Tumor Lysis Syndrome can be seen 48-72 hours after chemotherapy or from rapid cell turnover in the setting of lymphomas Renal injury takes place through uric acid precipitation in the acidic environment of the tubules Serum uric acid levels are often

> 15-20 mg/dL and urine uric acid levels >600 mg/24h [11] Also, hyperphosphatemia can lead to calcium-phosphate crystal formation and renal deposition [2] A urine uric acid to urine creatinine ratio >1.0 indicates a high risk of acute kidney injury [11]

Iodinated contrastinduced nephropathy

This is the third leading cause of acute renal failure in hospitalized patients and is caused by both renal vasoconstriction and tubular injury [5] Renal injury becomes apparent as rising serum creatinine within 72 hours after contrast administration [6] Risk factors include preexisting renal dysfunction, heart failure, diabetes, volume depletion, multiple myeloma, large volume and high osmolarity contrast

administration Preventative measures include premedication with isotonic saline volume infusion and/or N-acetylcysteine However, the KDIGO guidelines discourage using N-acetylcysteine to prevent AKI in critically ill or postsurgical patients with hypotension

Acute interstitial nephritis

Acute interstitial nephritis (AIN) is an interstitial inflammatory process that occurs mostly through cell-mediated immune reactions [11] It is often caused by medications (70% of cases) or infections (usually viral or atypical pathogens) [6].It usually presents without oliguria and the classic triad of rash, eosinophilia and fever is rarely seen Urinary sediment is routinely positive for white blood cells, white blood cell casts and eosinophils (detected with Hansel’s stain) [6] Renal biopsy may be needed for a definite diagnosis [2]

Drugs responsible for interstitial nephritis include antibiotics (aminoglycosides, amphotericin B, beta-lactams, fluoroquinolones, sulfonamides, vancomycin), anti-epileptics (carbamazapine, phenobarbital, phenytoin), NSAIDs (aspirin, ibuprofen, ketorolac, naproxen), diuretics (acetazolamide, furosemide, thiazides), acetaminophen, ACE-inhibitors, iodinated dyes, and ranitidine [6]

Obstructive nephropathy

Obstructive nephropathy accounts for 10% of the cases of acute kidney injury [6] Although obstruction can occur anywhere in the urinary tract, bilateral obstruction (or unilateral obstruction in a single functioning kidney) is necessary for a reduction in glomerular filtration rate to take place [3] If left untreated, obstructive nephropathy can lead to irreversible tubulointerstitial fibrosis [3]

Staging of AKI

The RIFLE criteria, which is used to define the severity of AKI:

-Risk: 1.5 fold rise in the serum creatinine, a 25% reduction in glomerular filtration rate (GFR), or a urine output below 0.5 ml/kg/

hr for six hours

-Injury: Two fold rise in the serum creatinine, a 50% reduction in GFR, or a urine output <0.5 ml/kg/hr for 12 hours

-Failure: Threefold rise in serum creatinine, a 75% reduction in GFR, or a urine output <0.3 ml/kg/hr for 24 hours, or anuria for 12 hours

-Loss: Complete loss of kidney function (e.g., need for renal replacement therapy) for > 4 weeks

-End stage renal disease (ESRD): Complete loss of kidney function (e.g., need for renal replacement therapy) for >3 months [12]

The Kidney Disease Improving Global Outcomes (KDIGO) foundation does not use GFR for staging:

-Stage 1: serum creatinine of 1.5-1.9 from baseline, ≥ 0.3 mg/dL (≥ 26.5 micromole/L) rise in serum creatinine, or urine output <0.5 mL/kg per hour for 6 to 12 hours

-Stage 2: serum creatinine of 2.0-2.9 or urine output <0.5 mL/kg per hour for ≥ 12 hours

-Stage 3: serum creatinine >3.0, urine output <0.3 mL/kg per hour for ≥ 24 hours, anuria for ≥12 hours, renal replacement therapy necessitation, age below 18 years, or a reduction decrease in estimated GFR to <35 mL/min per 1.73m2 [12]

Patients should be classified according to the criteria that result in the highest (most severe) stage of injury [12] Nevertheless, there are limitations to these criteria; for example in the early stages of AKI; the serum creatinine level does not correlate with the degree of renal injury [4] Another example would be patients with sepsis have decreased creatinine production; hence the serum creatinine level will not accurately reflect the degree of renal injury [4] Also, in patients with rhabdomyolysis, creatinine release from skeletal muscle adds to serum creatinine and therefore will not accurately reflect the degree of renal injury [2]

Management of AKI

In all cases of AKI, treating the underlying cause and discontinuation of all offending agents is the first step in management However, this may not always be possible in the ICU setting Secondly, initiation of volume resuscitation is important for volume expansion using isotonic crystalloid fluids, or in the case of hemorrhagic shock, colloid fluids [1] The early initiation of fluid therapy can also identify patients with pre-renal kidney injury if renal function responds quickly [1] Fluid resuscitation should be directed towards an objective physiologic endpoint, such as mean arterial pressure or urine output [13] The KDIGO guidelines recommend using vasopressors in conjunction with fluids in patients with shock irresolute with fluid resuscitation [1] Norepinephrine is currently the vasopressor of choice, as it raises mean arterial pressure without increasing mortality and without the accompanying arrhythmic events associated with dopamine [1]

Patients with all cases of AKI can develop hyperkalemia, metabolic acidosis, hypocalcemia and hyperphosphatemia In general, patients with AKI should avoid receiving medications containing potassium Hyperkalemia should be treated as medically indicated Patients with refractory hyperkalemic metabolic acidosis in the setting of volume overload or severe acidosis (PH<7.1) often necessitate renal replacement therapy Bicarbonate infusion in patients with metabolic acidosis and oliguria/anuria should be avoided as it can reduce ionized calcium and increase the partial pressure of carbon dioxide and intracranial pressure in patients with diabetic ketoacidosis Hypocalcemia and hyperphosphatemia are also commonly seen in AKI, and hypocalcemia should only be treated in symptomatic patients unless the serum phosphate level is >8 mg/dL, in which case the patient should be dialyzed due to the risk of calcium-phosphate binding and deposition in organs and vessels [13]

In the setting of cardiorenal syndrome, optimizing cardiac function is goal In critically ill patients, treatment is directed at establishing volume hemostasis through the use of intravenous (IV) loop diuretics, even if it leads toa temporary worsening of renal function Thiazide diuretics can be added in patients who are refractory to loop diuretics Ultrafiltration is only indicated in cases refractory to IV diuretics, not as first line, as studies have shown better outcomes with the use of diuretics [8]

In the case of hepatorenal syndrome in the ICU, it is usually managed with a combination of norepinephrine and albumin [2] Norepinephrine is given as a continuous infusion (0.5 to 3 mg/hr) with the goal of raising the mean arterial pressure by 10 mmHg,

and albumin is given as 1 g/kg per day for 2 days (maximum of 100 g per day) [10] In patients with spontaneous bacterial peritonitis, albumin infusion may prevent development of hepatorenal syndrome [2]

Patients with rhabdomyolysis induced renal failure should be treated with vigorous hydration (may require up to 10 L of normal saline during 24 hr), however, 30% of the patients will require dialysis [6] Patients with Tumor Lysis syndrome will also require vigorous hydration as well as allopurinol and rasburicase [2]

In the setting of ATN, there are experimental studies that suggest that the administration of growth factors insulin like growth factor-I (IGF-I), epidermal growth factor (EGF), and hepatocyte growth factor may expedite the recovery of renal function [5]

AIN is managed with the removal of the offending agent and/or treating the underlying infection [11] The use of steroids is controversial, but a treatment dose of methylprednisolone 0.5 to 1 g/d for one to four days or prednisone 60 mg/d orally for 1-2 weeks, followed by a prednisone taper can be used in severe cases [11] Complete resolution can take months [6]

However, in glomerular disease (which is less commonly seen in the ICU setting), treatment includes immediate intravenous corticosteroids (methylprednisolone at 7 mg/kg/day for 3 days followed by oral prednisone at 1 mg/kg/day up to 60 mg) and with cytotoxic immunosuppressants (cyclophosphamide at 2 to 3 mg/kg/day) Goodpasture’s disease often requires plasma exchange for therapy In TTP, plasma volume exchange is the lifesaving therapy, whereas antibiotics and platelets transfusion are contraindicated [2]

Renal Replacement Therapy

Renal replacement therapy (RRT) is indicated in the setting of refractory fluid overload, electrolyte abnormalities (especially hyperkalemia and hypocalcemia), metabolic acidosis, and uremic encephalopathy, as well as certain drug intoxications [14] In the ICU setting there are different forms of RRT; intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) but CRRT is becoming more favorable due to it being more physiologic-like and is better tolerated in critically ill patients [6] There have been studies to suggest that CRRT can also have an advantage in septic patients due to better removal of inflammatory mediators and an advantage in the cases of fulminant hepatic failure and acute brain injury due to hypothesized better cerebral perfusion [14] Nevertheless, there is no evidence to support that one method is associated with better outcomes compared to the other [15] The timing for initiation of RRT continues to be controversial; there are no definitive criteria at which RRT should be initiated, however, it

is recommended to initiate RRT prior to the development of life threatening symptoms or complications [14] Once there is evidence

of renal function improvement; continuous decrease in creatinine, an increase in urine output, electrolyte stabilization, symptomatic improvement and an improvement in creatinine clearance, then RRT can be discontinued [15]

Conclusion

We present the common causes of acute kidney injury in an ICU setting, from pre-renal to renal and post-renal anomalies Regardless

of the type of renal disease, identifying the underlying disorder is imperative in order to adequately manage the critically ill patient and prevent further complication Renal disease is an exceptionally common problem in an ICU setting and providers should be familiar with the clinical features and management strategies

References

1 Kellum JA, Lameire N; for the KDIGO AKI Guideline Work Group (2013) Diagnosis, evaluation, and management of acute kidney injury:

a KDIGO summary (Part 1) Crit Care 17: 204

2 Li Tingting and Anitha Vijayan (2012) “Acute Kidney Injury” The Washington Manual of Critical Care In: Wolters Kluwer Health/Lippincott Williams & Wilkins, (2nd ed) 351-65, Philadelphia

3 Hsu Chi-yuan (2013) “Diagnostic Approach to the Patient with Acute Kidney Injury (acute Renal Failure) or Chronic Kidney Disease”, Pedram Fatehi and Waltham, UpToDate

4 Palevsky PM, Liu KD, Brophy PD, Chawla LS, Parikh CR, et al (2013) KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury Am J Kidney Dis 61: 649-672

5 Okusa Mark D (2013) “Possible Prevention and Therapy of Postischemic (ischemic) Acute Tubular Necrosis”, Scott Sanoff and Waltham, UpToDate

6 Marino Paul L and Kenneth M Sutin (2007) “Oliguria and Acute Renal Failure.” In: The ICU Book- Lippincott, Williams & Wilkins,

10 Runyon Bruce A (2013) “Hepatorenal Syndrome”, Waltham, UpToDate

11 McPhee, Stephen J, Maxine A Papadakis, and Michael W Rabow (2012) “Kidney Disease.” In: Current Medical Diagnosis & Treatment (51st ed), McGraw-Hill Medical 880-84, New York

12 Palevsky Paul M (2013) “Definition of Acute Kidney Injury”, Waltham, UpToDate

13 Rosner, Mitchell H, (2013) “Overview of the Management of Acute Kidney Injury (acute Renal Failure)” Mark D Okusa and Waltham, UpToDate

14 Palevsky Paul M (2013) “Renal replacement therapy (dialysis) in acute kidney injury (acute renal failure) in adults: Indications, timing, and dialysis dose”, Waltham, UpToDate

15 Tolwani A (2012) Continuous renal-replacement therapy for acute kidney injury N Engl J Med 367: 2505-2514

Nutritional Support in an ICU Setting

Key Points:

1 ICU admission is a risk for malnutrition

2 Malnutrition is a risk factor for poor outcomes, increased length of stay and increased healthcare costs

3 A nutritional assessment should be made daily on all ICU patents

4 Enteral feeding within 24-48 hours of ICU admission should be the goal for the majority of ICU patients

5 Parenteral nutrition and specialized formulas may be indicated in select patient groups

6 Nutritional therapies should be monitored closely for complications such as re-feeding syndrome

7.When managing critically ill patients, a multi-faceted team approach to nutrition should include a member trained in nutritional support

There are some indications for parenteral nutrition and specialized formulas; however, the routine use of either of these therapies

is not recommended All patients receiving nutritional support should be monitored for tolerance and complications associated with the therapy Nutritional assessment and delivery is optimal when done by a multi-disciplinary team that includes a specialist in nutrition [1]

Nutritional Assessment

Loss of body and muscle mass during a critical illness is associated with decreased survival and delays in recovery and rehabilitation after ICU discharge [1] The Joint Commission on Accreditation of Healthcare Organization (JCAHO) mandates a nutritional screening within 24 hours of hospital admission Nutritional screening can determine if the patient is malnourished, or

at risk of malnourishment, with screening risk factors [2]

Nutritional evaluation is a global assessment of both nutritional status and severity of illness because of the fundamental relationship between the two Hospital admission is a risk factor for detritions in nutritional status resulting in loss muscle mass in about a third of all hospitalized patients A major factor associated with malnutrition in the ICU is a nil per os (NPO) order typically placed for diagnostic tests or surgery Interruptions in nutrition are common in the intensive care unit and consequently promote insulin resistance in addition to weight loss [1] The preservation of lean body mass when patients leave the ICU plays a key role in recovery and regaining long-term function

A complete nutritional history is the first step in nutritional risk assessment During an acute illness, it is often difficult to obtain

a detailed history However, every attempt should still be made to obtain patient information, even if obtained indirectly from family members Any patient staying in the ICU over 2 days without normal oral intake is at a risk of malnutrition The nutritional history has three key indicators:

The Nutritional Risk Screening (NRS)-2002 is often used for hospitalized patients; however, it does not provide usable information

in the assessment of nutritional risk in the ICU When assessing nutritional risk, one should include consideration of shock, motility disorders, and intra-abdominal hypertension The ultimate goal should be to feed patients within 24 to 48 hours of ICU admission

Christina Lipay 1 * , Paul J McCarthy 2 and Laura E Matarese 3

1 RD, LDN, Vidant Medical Center, USA

2 MD, East Carolina University – Brody School of Medicine, Department of Internal Medicine, Section of Pulmonary, Critical Care and Sleep Medicine, USA

3 PhD, RD, LDN, CNSC, FADA, FASPEN, Associate Professor, East Carolina University – Brody School of Medicine, Department of Internal Medicine, Section

of Gastroenterology, Hepatology and Nutrition, USA

*Corresponding author: Vidant Medical Center, USA, Tel: (252)845-5114;

with enough calories and nutrients to meet the needs of the patient without causing complications such as re-feeding syndrome (to be discussed later)

Nutritional Support

In a critical illness, hyper-metabolism in conjunction with nutritional deprivation can quickly lead to malnourishment Malnutrition,

as a result of a preexisting condition or acute illness, significantly increases the risk of a poor outcome Malnourishment is associated with increased risk of infections, prolonged mechanical ventilation, and ICU and hospital length of stay [3] Early initiation of enteral nutrition is associated with improvement in intestinal absorption and clinical outcomes Barriers to nutritional support include disease state, NPO status for procedures and tests, and physician bias The “too sick to feed” philosophy is an all too common practice

Despite the many positive clinical impacts associated with optimal nutritional support, its’ importance is often underappreciated and many clinical questions remain unanswered For example, the optimal goal for caloric deliver is unclear and there is mixed data on the benefits of many specialized formula and supplements [3]

Enteral Nutrition

Enteral nutrition is an ideal feeding solution to maintain gut integrity if a patient has a functioning gastrointestinal tract but is unable

to safely swallow and orally consume nutrients Enteral nutrition should be initiated within 24-48 hours of an ICU admission [4], and may be started despite the absence of bowel sounds in hemodynamically stable patients It may also be initiated or continued with the presence of a mild to moderate ileus [4,5] The greatest benefit of early enteral nutrition is achieved with 50-65% of the target goal volume being met within the first week of hospitalization [6] When feeding a critically ill patient, early initiation of enteral nutrition has various benefits that include sustaining gut barrier function, preventing microbial invasion, resuming normal digestion and absorption and reducing metabolic response to stress Early nutritional support therapy may reduce disease severity with reduction in complications and decreased lengths of ICU stay [4]

Predictive equations determine a critically ill patient’s calorie and protein requirements in the absence of indirect calorimetry It is essential to obtain an accurate height and weight to calculate body mass index (BMI) and estimate nutritional needs Adults with normal

or overweight BMI of 18.5-29.9 kg/m2 require 20-30 kcal/kg actual body weight per day Protein requirements for this population should range between 1.2-2.0 g/kg actual body weight daily Providing additional protein may delay or prevent further lean body mass breakdown

in the setting of critical care inactivity and prolonged hospitalization days Multiple factors contribute to protein loss, including trauma, infection, burns, surgery, wounds, bed rest and medications [7] Catabolic and severely stressed patients with multiple trauma sites and burns require additional protein up to 2.5 g/kg daily

Providing a hypocaloric, protein sparing feeding regimen is recommended for critically ill obese patients Contrary to popular belief, obesity does not ward off malnutrition due to additional fat stores and body habitus Poor fuel utilization, futile cycling issues and insulin resistance may predispose patients to protein degradation and greater loss of lean body mass, leading to sarcopenic obesity [8-10] Hypocaloric and protein-rich diets decrease risks of infection and hospital length of stay compared to eucaloric feeds [7] Furthermore, underfeeding an obese patient boosts fat mass loss, while improving insulin sensitivity [5,8] The goal for a critically ill obese patient should be to avoid exceeding 60-70% of the estimated nutritional needs by providing 22-25 kcal/kg ideal body weight or 11-14 kcal/

kg actual body weight daily Ideal body weight for females is calculated as 100 pounds for the first five feet in height, with the addition

of five pounds for each exceeding inch Ideal body weight for males is calculated as 106 pounds for the first five feet in height and six pounds for each additional inch General nutritional goals are to provide ≥2.0 g/kg ideal body weight daily of protein for patients with a BMI of 30-40 kg/m2 (class I and II) and ≥2.5g/kg for BMI ≥40 kg/m2 (class III) In addition, patients that are receiving hemodialysis or continuous renal replacement therapy have increased protein requirements of up to 2.5 g/kg daily Avoid restricting protein in patients with liver failure [6]

Once estimated calorie and protein needs are determined, the appropriate formula should be determined For example, a polymeric 1.5 kcal/ml solution is the formula chosen to feed a newly intubated patient The estimated goal energy needs of this patient are 1,800 calories Determine the total volume needed daily: 1800 divided by 1.5, as this is the calorie density of Isosource 1.5 (1.5 kcal/mL) Next, divide the quotient by 24 hours to determine the continuous feeding goal rate The ultimate goal volume is 50mL/hr

Continuous infusion of enteral nutrition is often the suggested frequency for feeding critically ill patients [7] Bolus feedings are generally not recommended for critically ill patients due to the risk of intolerance and aspiration [7] However, a patient may be transitioned to an intermittent, nocturnal or bolus-feeding regimen as they clinically improve

Starting enteral nutrition at a minimal rate is recommended to monitor tolerance closely A low rate of 10-30 mL/hr can be initiated

as tolerated by the patient’s medical condition [4] In an intubated and/or sedated patient in the intensive care unit setting, 10mL/hr is often ordered once the decision is made to enterally feed [4] Trophic feedings, or the practice of feeding a small hourly volume, do not provide a significant source of calories and nutrients Nevertheless, this is likely a safe method to maintain gut integrity and monitor the ability to advance towards the goal rate The feeding can be advanced 10mL every 4-6 hours to the goal rate Slower advancement may

be warranted with certain conditions and circumstances such as gastrointestinal intolerances, risk of refeeding syndrome and medical instability

Caution should be practiced when initiating enteral nutrition in a hemodynamically unstable patient requiring vasopressors A marginally perfused gut can be further exacerbated with the initiation of enteral nutrition and the metabolic efforts of absorption [7] Occasionally, trophic enteral nutrition will be initiated and monitored closely in patients at increased risk of aspiration As arterial blood pressure and hemodynamic stability improves and requires less vasoactive agents, the rate and volume of enteral nutrition can be increased towards a goal rate as tolerated

Additional sources of calories (i.e dextrose intravenous fluids, propofol, dialysate solutions) should not be overlooked Dextrose infusions provide 3.4 calories per gram Thus, D5W @ 100mL/hr continuously provides 120g dextrose x 3.4 kcal/g totaling 408 kcals daily Propofol contains a 10% lipid emulsion, which provides 1.1 kcal/mL Propfol infusion should be monitored for extended use and included in the overall nutrition equation Clevidipine (cleviprex) is formulated as a 20% lipid emulsion providing 2 kcal/mL Lipid restrictions may be warranted for patients with significant lipid metabolism disorders In addition, 60-70% of dextrose absorption can be calculated from the total volume of dialysate solution received

Fluid requirements must be addressed in the ICU, as patients may receive unrecognized fluid(s) from multiple sources, including intravenous resuscitation, medication co-formulations, enteral nutrition free water formulas, and free water flushes Hydration and fluid volume should be closely monitored, as organ failure, diuresis and increased fluid losses are especially common in the ICU Free water flushes with a minimum of 30-50mL every 4-6 hours are ideal to assist in meeting a patient’s fluid requirement and to prevent blockage

of a gastric feeding tube

Short term feeding tubes can be inserted nasally or orally and terminate in the stomach, duodenum or jejunum An oral tube terminating in the stomach is appropriate for a critically ill, intubated patient Post-pyloric termination and placement distal to the ligament of Treitz may be warranted in certain scenarios such as pancreatitis, gastric dysmotility and recurrent emesis This can be achieved with a small bore, flexible tube with a weighted tip that can terminate in the appropriate location Feeding tubes may be placed incorrectly, increasing the risk for aspiration and perforation Short term feeding tubes can be placed at the bedside and placement should

be confirmed by x-ray Should enteral nutrition be expected for over four weeks of time, placement of a gastrostomy, jejunostomy or gastrojejunostomy tube may be indicated

Specialized Formulas

Enteral nutrition formulas vary with calorie and protein density, fiber content, and source of macro and micronutrients Standard formulas should be used in the ICU Specialized formulas are designed for specific disease states and conditions; however they have little impact in the majority of patients [7] Standard, polymeric formulas are nutritionally complete for patients that are able to tolerate unaltered molecules of macronutrients and can absorb nutrients without difficulty Standard formulas have a caloric density of 1.0-2.0 calories/mL and may contain fiber to help support normal bowel function

Elemental-type or predigested formulas may be better tolerated with minimal digestion requirements for patients with impaired gastrointestinal function Such conditions include pancreatitis, chronic diarrhea, malabsorption, Crohn’s disease, irritable bowel disease, short-bowel syndrome, and those transitioned from parenteral nutrition Elemental formulas contain a balanced amino acid and peptide profile from hydrolyzed, predigested protein In addition, the majority of the fat content is from medium chain triglycerides, decreasing the potential for fat malabsorption A variety of elemental formulas designed and marketed for specific clinical situation exist

Specialized formulas such as those designed for renal disease, diabetes, pulmonary disease, hepatic disease and immunocompromised individuals can address and often prevent exacerbations of certain conditions For examples, renal formulas with low in electrolytes and high protein formulations are ideal for patients on dialysis, while calorically dense renal formulas with restricted protein are ideal for those that are not on renal replacement therapy but require fluid restriction A change from a standard formula to a specialty formula

is warranted if electrolyte abnormalities exit or develop [3] Modular protein can be added to a tube feeding regimen to better meet a patient’s nutritional needs

Parenteral Nutrition

Parenteral nutrition can supply calories to malnourished patients and has been associated with improved outcomes in specific patient populations that will be discussed later in this section Parenteral nutrition is not without risks and in many ICU patients can even be harmful The purpose of this section is to include an introduction to parenteral nutrition and not an exhaustive review, as the topic can be relatively complex One should understand that parenteral nutrition is not a benign therapy and a trained specialist should be participating in the specific indications and prescription of parenteral nutrition

In a previously healthy, well-nourished subject in whom enteral nutrition cannot be used, parenteral nutrition should be held for a minimum of 7 days [7] However, in patients with evidence of protein-calorie malnutrition upon admission, it may be appropriate to initiate parenteral nutrition once resuscitated if enteral administration is not feasible In patients undergoing gastrointestinal surgery and enteral nutrition is contraindicated, parenteral nutrition should be started 5 to 7 days prior to surgery and continued post-operatively [7]

In post-operative patients not already on parenteral nutrition, parenteral therapy should be delayed in well-nourished patients for 5 to 7 days if enteral nutrition is not practicable There is little-to-no benefit of giving parenteral nutrition for less than 7 days and thus, persons expected to tolerate enteral nutrition by the 7th post-operative day should not receive parenteral nutrition [7]

In ICU patients receiving parenteral nutrition, permissive underfeeding to a goal of 80% of nutritional requirements should be considered [1] Once the patient is clinically stable and tolerating parenteral nutrition, a slow titration of parenteral nutrition to the nutritional goal should then be done During the first week of parenteral nutrition in the ICU setting, it is recommended to use parenteral glutamine formulations without soy-based lipids [7] Periodic efforts should be made to initiate enteral feedings in patients on parenteral nutrition As enteral nutrition is increased, parenteral nutrition should also be reduced [7]

Monitoring of Nutritional Therapy

Continuous monitoring is warranted for a patient receiving nutritional support in order to evaluate whether the estimated nutritional needs are being met Should impediments be determined, a restructured plan needs to be implemented to meet the overall nutrition goal Avoidance and cessation of unnecessary tube feeding is vital in critically ill patients Gastric dysmotility with delayed emptying

is common in the ICU, with multifactorial etiologies including hyperglycemia, medication effects, electrolyte abnormalities, elevated intracranial pressures, hyperosmolar formulas and sepsis [7,11]

Avoid holding enteral nutrition for <500mL of gastric residuals in the absence of other signs of intolerance [6] In the presence

of elevated gastric residuals, consider prokinetic agents or a more concentrated tube feeding formula to be infused at a lower rate In the event of continuous high gastric residual volumes, placing a feeding tube below the ligament of Treitz may be considered Gastric residuals do not need to be assessed when enteral nutrition is infused through a small bore feeding tube

It is important to avoid aspiration by elevating the head of the patients’ bed to 30-45 degrees For patients that are at risk of aspirating, continuous feedings, prokinetic drugs and post-pyloric feedings should be considered [6] As oropharyngeal secretions can be aspirated, research to support feeding directly into the small bowel as a method to decrease the risk of aspiration is inconclusive [4] During emesis episodes, providers should hold enteral nutrition and restart and monitor tolerance closely at a lower rate when possible In the event of severe intractable vomiting, the need for parental nutrition should be carefully evaluated

Diarrhea is defined as greater than 500 mL of stool output per day or >1,000 mL of output from an ileostomy [4,8] Avoid inappropriate cessation of enteral nutrition in the occurrence of diarrhea and rule out infectious and medicinal causes Antibiotic-associated diarrhea,

including Clostridium difficile colitis, should not be mistaken for osmotic diarrhea Collect stool specimens for Clostridium difficile

sampling prior to initiating any antimotility agents In addition to sorbitol preparations used as elixirs, histamine H2-receptor antagonists, and proton pump inhibitors, additional factors that may cause diarrhea include reduced absorptive surfaces, bacterial overgrowth and gastric or colonic hypersecretion [4,7] The actual formula and/or formulary delivery system may be bacterially contaminated and cause diarrhea An enteral nutrition formula may be hyperosmolar and/or have inadequate fiber to form bulk, excessive fiber, or high fat content in the presence of fat malabsorption syndromes [12,13] Diarrhea can also result from the rapid advancement in enteral nutrition rate, in which case the rate should be reduced and recalibrated as tolerated Modifying a standard or specialized formula to an elemental formula or alternating between fiber-free and fiber containing formulas can be considered when diarrhea is due to enteral nutrition intolerance

Diarrhea output sometimes may be managed and reduced without medication Increasing soluble fiber may be helpful in stable ICU patients with diarrhea receiving enteral nutrition [6] Soluble fiber formulations and bulk forming fibers (i.e psyllium) can thicken stool consistency and decrease colonic transit time While the use of probiotics in replacing gastrointestinal microbiota has been described, data remains limited and controversial [6]

An enterally fed critically ill patient should also be monitored for metabolic complications, including hyperglycemia and fluid or electrolyte imbalances Effective monitoring and control of blood glucose is vital Moderate glucose control should be kept below 180 mg/dL [5]

Refeeding syndrome is a metabolic and clinical syndrome that may result when a carbohydrate infusion is aggressively initiated with a malnourished patient An intracellular shift of glucose and electrolytes as a result of insulin secretion can lead to dangerously low levels of serum potassium, phosphorous and magnesium, potentially resulting in respiratory, cardiac, skeletal, neurologic, endocrine, hematologic, metabolic, and/or gastrointestinal complications Severe consequences also include seizures, paralysis, cardiac dysfunction, and respiratory failure with ventilator dependency or death [14]

Refeeding syndrome is preventable but requires keen awareness and identification of patients at risk It is crucial to understand a patient’s nutrition history, including dietary patterns, weight changes and barriers from receiving adequate nutrition prior to admission High risk patients often have one or more of the following: BMI <16, unintentional weight loss >15% over the previous 3-6 months, poor nutritional intake for >10 days, and/or low levels of potassium, phosphate or magnesium prior to the initiation of feeding [15]

A patient is considered high risk when ≥2 of the following are present: BMI <18.5, unintentional weight loss > 10% within 3-6 months prior to admission, suboptimal nutritional intake for >5 days, or a history of alcohol abuse or use of insulin, chemotherapy, antacids or diuretics medications [16-20] Therefore, the nutritional re-introduction in patients at high risk for refeeding syndrome should be done carefully It is imperative to replete slowly, initiating enteral nutrition at 10mL/hr, and provide 1,000 kcal/day or 15-20 kcal/kg/day for adults within the first 1-3 days Enteral nutrition may continue to advance, reaching the goal rate within 5-7 days of initiation Monitor phosphorous, magnesium and potassium daily and replete as warranted [20]

Malnourished patients are also at risk for vitamin deficiencies Deficiency in thiamine, an essential coenzyme in carbohydrate metabolism, can occur in less than 28 days in patients with inadequate nutritional intake and should be supplemented to prevent Korsakoff’s syndrome and Wernicke’s encephalopathy [15,18,19]

Conclusion

In general, enteral feeding within 24 to 48 hours of ICU admission should be a goal for critically ill patients Patients admitted to the ICU are frequently at risk of malnutrition and therefore should have routine nutritional assessments Once a nutritional plan is in place, the patients should be followed for enteral feeding tolerance and complications There are limited, but important, roles for parenteral nutrition and specialized formulas in the ICU Nutritional therapies are best delivered with the input of a specialist trained in nutrition

References

1 Chapman MJ, Nguyen NQ, Deane AM (2011) Gastrointestinal dysmotility: clinical consequences and management of the critically ill patient Gastroenterol Clin North Am 40: 725-739.

2 Hiesmayr M (2012) Nutrition risk assessment in the ICU Curr Opin Clin Nutr Metab Care 15: 174-180.

3 Mueller C, Compher C, Ellen DM; American Society for Parenteral and Enteral Nutrition (AS.P.E.N.) Board of Directors (2011) A.S.P.E.N clinical guidelines: Nutrition screening, assessment, and intervention in adults JPEN J Parenter Enteral Nutr 35: 16-24.

4 The A.S.P.E.N (2012) Adult Nutrition Support Core Curriculum, (2ndedn): 171-183

5 Ukleja A, Freeman KL, Gilbert K, Kochevar M, Kraft MD, et al (2010) Standards for nutrition support: adult hospitalized patients Nutr Clin Pract 25: 403-414.

6 McClave SA, Martindale RG, Vanek VW, McCarthy M, Roberts P, et al (2009) Guidelines for the Provision and Assessment of Nutrition Support Therapy

in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) JPEN J Parenter Enteral Nutr 33: 277-316.

7 Martindale RG, McClave SA, Vanek VW (2009) Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition: Executive Summary* Crit Care Med 37: 1757-1761

8 Miller KR, Kiraly LN, Lowen CC, Martindale RG, McClave SA (2011) “CAN WE FEED?” A mnemonic to merge nutrition and intensive care assessment of the critically ill patient JPEN J Parenter Enteral Nutr 35: 643-659.

9 McClave SA, Kushner R, Van Way CW 3rd, Cave M, DeLegge M, et al (2011) Nutrition therapy of the severely obese, critically ill patient: summation of conclusions and recommendations JPEN J Parenter Enteral Nutr 35: 88S-96S.

10 Honiden S, McArdle JR (2009) Obesity in the intensive care unit Clin Chest Med 30: 581-599, x.

11 Port AM, Apovian C (2010) Metabolic support of the obese intensive care unit patient: a current perspective Curr Opin Clin Nutr Metab Care 13: 184-191.

12 Gottschlich MM (2007) The A.S.P.E.N Nutrition Support Core Curriculum: A Case-Based Approach- The Adult Patient American Society for Parenteral and Enteral Nutrition Silver Spring, MD

13 Kulick D, Deen D (2011) Specialized nutrition support Am Fam Physician 83: 173-183.

14 Eisenberg P (2002) An overview of diarrhea in the patient receiving enteral nutrition Gastroenterol Nurs 25: 95-104.

15 Mehanna HM, Moledina J, Travis J (2008) Refeeding syndrome: what it is, and how to prevent and treat it BMJ 336: 1495-1498.

16 McCray S, Walker S, Parrish CR (2005) Much ado about refeeding Pract Gastroenterol 29: 26, 31–37

17 Mehanna H, Nankivell PC, Moledina J, Travis J (2009) Refeeding syndrome awareness, prevention and management Head Neck Oncol 1: 4.

18 National Institute for Health and Clinical Excellence Nutrition support in adults (2006) Clinical guideline CG32

19 Romanski SA, McMahon MM (1999) Metabolic acidosis and thiamine deficiency Mayo Clin Proc 74: 259-263.

20 Yantis MA, Velander R (2008) How to recognize and respond to refeeding syndrome Nursing 38: 34-39.

An ICU Bedside Review of Burns

Introduction

The therapy of burn injuries has been described since the time of the ancients [1] The evolution in our understanding of burn management has progressed rapidly over the past century, with standards of care in burn management now well established This chapter will summarize the current management recommendations of burn injuries

Emergency Triage

The initial evaluation of a seriously burned patient consists of a primary and secondary survey approach advocated by the American College of Surgeons Committee on Trauma’s Advanced Trauma Life Support The primary survey is focused on initial stabilization (airway, breathing, circulation, disability assessment and adequate exposure) while the secondary survey provides a more detailed attention to the burn injury location, extent and depth Superficial or first-degree burns should not be included when calculating the percent of total body surface area (TBSA), and thorough cleaning of soot and debris is mandatory to avoid confusing areas of soiling with burns Table 1 presents a potential approach to evaluating a seriously burned patient

Step 1 Primary Survey Vascular access and volume resuscitation Step 2 Inhalation Injury Pulse oximetry, oxygenation Step 3 Secondary Survey History and head-to-toe physical

examination Step 4 Estimate Burn Size Lund-Browder diagram or “Rule of Nines”

(Figure 1) Step 5 Estimate Burn Depth Serial wound examinations Step 6 Evaluate for other burns Electrical, chemical, drug burns Treat

accordingly Step 7 Evaluate need for antibiotics Treat according to susceptibility patterns Step 8 Evaluate for abuse Notify proper authorities

Table 1:Management Summary of Burns [2].

As this chapter involves care for critically ill adult patients, we have not included the diagram adjusting TBSA for children.

Figure 1: Rule of nines to determine total body surface area that has been burned [3].

With direct thermal injury to the upper airway or smoke inhalation, rapid and severe airway edema is a potential life-threatening complication Anticipating the need for intubation and establishing an early airway is critical Perioral burns and singed nasal hairs are signs that the oral cavity and pharynx should be further evaluated for mucosal injury However, these physical findings do not indicate

Nazia Sultana * and Abid Butt

East Carolina University – Brody School of Medicine, Department of Internal Medicine, Section of Pulmonary, Critical Care & Sleep Medicine, Greenville, NC

27834, USA

*Corresponding author: Nazia Sultana, East Carolina University –

Brody School of Medicine, Department of Internal Medicine, Section

of Pulmonary, Critical Care & Sleep Medicine, Greenville, NC 27834,

an upper airway injury in itself Signs of impending respiratory compromise may include a hoarse voice, wheezing, or stridor; subjective dyspnea is a particularly concerning symptom, and should trigger prompt elective endotracheal intubation In patients with concomitant multiple traumatic injuries, especially oral trauma, nasotracheal intubation may be useful but should be avoided if oral intubation is feasible

Classification of Burn Injury Based on Depth

Burn wounds are commonly classified as superficial (first degree), partial thickness (second degree), full thickness (third degree), and fourth-degree burns (in which the underlying soft tissue affected) [4] Partial-thickness burns are then sub-classified by depth of involved dermis to either superficial or deep partial thickness burns First-degree burns are painful but do not blister, while second-degree burns have dermal involvement and are extremely painful with weeping and blistering Third-degree burns are generally hard, painless, non-

blanching lesions.Jackson described three zones of tissue injury following burn injury [4] The zone of coagulation is the most severely

burned portion and is typically in the center of the wound As the name implies, the affected tissue is coagulated and sometimes necrotic,

often requiring excision and grafting Peripheral to coagulation zone is the zone of stasis, which has a local response of vasoconstriction

and resultant ischemia Appropriate resuscitation and wound care may help prevent conversion to a deeper wound, but infection or suboptimal perfusion may result in an increased burn depth This is clinically relevant, as many superficial partial-thickness burns will heal with expectant management, while the majority of deep partial-thickness burns require excision and skin grafting The last area of a

burn is called the zone of hyperemia, which will heal with minimal or no scarring.

Fluid Resuscitation

As accurate estimation of a burn injury is crucial in guiding appropriate therapy, the size and depth are used as the prime determinants

of burn severity The well-known rule of nines provides a quick estimate of burn extent, while the Lund-Browder chart [3], though more laborious, is more accurate at quantifying the burnt TBSA The Parkland or Consensus formula is the most widely used tool to estimate the fluid resuscitation requirement in the first twenty-four hours after burn It suggests administering volume resuscitation at 4 ml/kg/TBSA, half of which is given in the first 8 hours post-injury and the remaining half in following16 hours Traditionally, lactated ringers have been the resuscitating fluid of choice as colloids may result in increased mortality [5] Current guidelines do not recommend the use

of either hypertonic solutions or fresh frozen plasma, unless specifically indicated

meta-“systemic inflammatory response syndrome” (SIRS) in burns patients as they are in a state of chronic inflammation Instead, they advocate using the modified criteria to define sepsis in these patients [9] When an infection is suspected, local pathogen resistance patterns should be taken into consideration when administering empiric antibiotics

Invasive device infections secondary to Staphylococcus aureus, enterococci, gram-negative bacteria, and candida are often the cause

of infection in patients with burns less than 30% of TBSA [6] Patients exposed to contaminated supplies or dusts during construction are at risk for Aspergillus infections Hydrotherapy equipment is discouraged due to its risk of gram-negative organism infections (i.e Pseudomonas, Acinetobacter) Instead, excision of burn wounds in an operating room setting is recommended At this time, there is no consensus on the most effective infection control practices and routine barrier precautions (i.e contact, droplet, standard precautions)

As with any infection control measure, hand washing is imperative A status of tetanus immunization should be sought and a tetanus booster should be administered in the emergency room if needed

Pain Management

Burns can produce excruciating pain, and thus aggressive analgesia with intravenous long and short-acting acting analgesics are recommended [10] It is also important to administer anxiolytic agents (i.e benzodiazepines) with the analgesics to help reduce long-term anxiety

Poisoning

Another important contributor to early mortality resulting from smoke inhalation is carbon monoxide (CO) poisoning [11] The affinity of CO for hemoglobin is approximately 200–250 times greater than oxygen Once bound to hemoglobin, it prevents the off-loading of oxygen in the peripheral circulation, which can quickly lead to anoxia and death Diagnosis requires an astute index of suspicion as the pulse oximtery and standard arterial blood gases (ABG) may not be diagnostic Arterial blood gas with co-oximetry will reveal an elevated CO-Hb level if present Treatment is by administering 100% oxygen, which effectively reduces the CO half-life from about 250 minutes to 60 minutes Hyperbaric oxygen may be appropriate for patients with serious exposure to CO (CO levels >25% with depressed mental status suspected secondary to carbon monoxide exposure) who are hemodynamically stable and not requiring ongoing resuscitation

Hydrogen cyanide toxicity may also be a cause of smoke inhalation injury Patients may have a persistent lactic acidosis or segment elevation on electrocardiogram Cyanide inhibits cytochrome oxidase, which in turn inhibits cellular oxygenation Treatment consists of sodium thiosulfate, hydoxocobalamin, and 100% oxygen Sodium thiosulfate works by transforming cyanide into a nontoxic thiocyanate derivative; however, it works slowly and is not effective for acute therapy Hydroxocobalamin is recommended for immediate therapy as it quickly complexes with cyanide and is excreted by the kidney In the majority of patients, the lactic acidosis will resolve with oxygenation and sodium thiosulfate treatment becomes unnecessary

When to Transfer Burn Patients

Specific criteria guide transfer of patients with more complex injuries or other medical needs to a burn center [5]:

References

1 Bryan CP (1930) The papyrus ebers.

2 Du Bois D, Du Bois EF (1989) A formula to estimate the approximate surface area if height and weight be known 1916 Nutrition 5: 303-311.

3 Lund C, Browder N (1944) The estimation of areas of burns Surg Gynecol Obstet 79: 352-358

4 JACKSON DM (1953) [The diagnosis of the depth of burning] Br J Surg 40: 588-596.

5 Saffle J (2001) Practice Guidelines for Burn Care J Burn Care Rehabil 22: 31

6 Siegel JD, Rhinehart E, Jackson M, Chiarello L; Health Care Infection Control Practices Advisory Committee (2007) 2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Health Care Settings Am J Infect Control 35: S65-164.

7 Avni T, Levcovich A, Ad-El DD, Leibovici L, Paul M (2010) Prophylactic antibiotics for burns patients: systematic review and meta-analysis BMJ 340: 341.

8 Endorf FW, Gibran NS (2010) Chapter 8 Burns In Schwartz’s Principles of Surgery, Brunicardi FC, Andersen DK, Billiar TR, Dunn DL, Hunter JG, Matthews

JB, Pollock RE (Eds).

9 Greenhalgh DG, Saffle JR, Holmes JH 4th, Gamelli RL, Palmieri TL, et al (2007) American Burn Association consensus conference to define sepsis and infection in burns J Burn Care Res 28: 776-790.

10 Faucher L, Furukawa K (2006) Practice guidelines for the management of pain J Burn Care Res 27: 659-668.

11 Hampson NB, Mathieu D, Piantadosi CA, Thom SR, Weaver LK (2001) Carbon monoxide poisoning: interpretation of randomized clinical trials and unresolved treatment issues Undersea Hyperb Med 28: 157-164.

Status Epilepticus

Brief overview

The traditional definition of Status Epilepticus (SE) is 30 minutes of sustained seizure or a period of 30 minutes in which a patient has more than one seizure without recovery from the post-ictal state Clinicians should understand that most seizures will terminate spontaneously within a few minutes and seizures that persist over five to seven minutes should almost always be treated; and for practical purposes are status epilepticus

The estimated incidence of Generalized Convulsive SE (GCSE) in the United States ranges from 50,000 to 250,000 cases/year [1] Most seizures in the ICU are non-convulsive and cannot be diagnosed by physical exam In dedicated Neurologic ICUs (NICU), non-convulsive seizures have been reported in 18% to 34% of those that undergo EEG monitoring and 10% are in Non-Convulsive Status Epilepticus (NCSE).The most common cause of SE is a prior history of epilepsy (usually associated with noncompliance) However, a significant proportion of SE occurs in patients without a history of seizures Other causes of seizures include cerebral hemorrhage, encephalitis, Cerebrovascular Accident (CVA), alcohol, drugs, and metabolic derangements Up to 10% of patients admitted to medical wards for non-neurologic diagnoses will have a seizure and this is most often NCSE (7) Although there is limited data, reports of up to a third of patients with altered consciousness are found to have non-convulsive seizures on EEG

Multiple risks factors for seizure can occur in the ICU, with patient pathology and medications covering most of the risk factors Anoxic encephalopathy, renal failure, autoimmune disorders, hyper or hypoglycemia, infections, sepsis, liver failure and stroke are a short list of pathologic processes that can be associated with seizures Some of the medications that can contribute to the development of seizures include antibiotics (especially beta-lactams), cyclosporine, theophylline, antipsychotics, diphenhydramine, and tramadol The likely cause of status epilepticus in a newly admitted general ICU patient may be noncompliance of antiepileptics, infection, and alcohol withdrawal or drug toxicity

Clinical features

Status epilepticus may be difficult to identify, especially in the ICU when factors such as an unknown neurologic baseline, sedation or delirium can blunt the neurologic examination Status epilepticus may present as frank tonic-clonic seizures or obtundation, or anything in between Moreover, non-convulsive status epilepticus is far more common in an ICU Patients that present with a tonic-clonic seizure and are treated with antiepileptic can appear to be asleep while instead they are in NCSE.About 20% of patients that have had clinical seizures terminated are in NCSE when the EEG is applied.Both convulsive status epilepticus and NCSE as prolonged seizures correlate with poor outcomes due to direct neuronal injury Systemic complications of convulsive status epilepticus include rhabdomyolysis, acidosis, renal failure, hyperthermia, arrhythmias, trauma, and aspiration

Diagnostic workup

Status epilepticus is a medical emergency The diagnostic workup and management should be done simultaneously The initial approach includes airway management, assessment of volume status, and concomitant antiepileptics Most patients should have the following tests and studies: Head computed tomography (CT), monitoring of vital signs, EEG (continuous if a suspicion of SE), metabolic panel, and magnesium Additional tests to consider based on clinical situation include magnetic resonance imaging (MRI), lumbar puncture, toxicology, coagulation, liver enzymes, and antiepileptic levels The importance of continuous EEG should

be stress as routine EEG only gives a brief snapshot of neurologic activity

Paul J McCarthy 1 * and Arash Afshinnik 2

1 East Carolina University- Brody School of Medicine, Department of Internal Medicine, Section of Critical Care Medicine

2 Oschner Health Systems, New Orleans, LA

*Corresponding author: Paul J McCarthy, MD, East Carolina

University- Brody School of Medicine, Department of Internal Medicine, Section of Critical Care Medicine, Greenville, NC 27834, Tel: +1 (318)

Management

The basic principles include (1) control of all seizure activity as soon as possible and (2) ensuring appropriate dosing of antiepileptics

to prevent recurrence of seizures Earlierinitiation of antiepileptic treatment allows for increased likelihoodof terminating the seizures Lorazepam has the most data supporting its use; followed by diazepam While these medications are often under-dosed in fear of associated respiratory depression, there is a higher risk of respiratory failure due to continued status epilepticus

Initial therapy should include lorazepam at a minimum 4 mg initial dose (occasionally 0.05 – 0.1 mg/kg) with repeat does every five minutes Diazepam 0.15 mg/kg and midazolam 0.2 mg/kg are acceptable alternatives Consider adding either valproic acid at 20 - 40 mg/kg IV with a target serum level of 15 – microgram/mL or phenytoin/fosphenytoin at 20 mg /kg phenytoin equivalents with a target serum level of 15 – 20 microgram/mL Additional dosing of 5 mg/kg of phenytoin may be given if a patient remains in status epilepticus Although fosphenytoin is associated with less phlebitis than phenytoin, it provides no other benefits Phenobarbital and levetiracetam are acceptable alternatives with levetiracetam being used with increased frequency Status epilepticus that continues despite treatment with two medications is considered refractory For patients continuing to be in SE after an infusion of midazolam or propofol, phenobarbital infusion should be considered Other potential therapies include lacosamide, ketamine, topirate, inhaled anesthetics and therapeutic hypothermia Patients in status epilepticus should be monitored with continuous EEG Generally once complete termination is achieved

on EEG for several hours infusions can be slowly decreased If seizure activity is noted on EEG, infusions are increased and antiepileptics are increased and/or additional agents are added

Post-tPA care

Generally, there are two groups of AIS patients admitted to the critical care unit The first group is obligated to spend at least 24 hours

in the ICU setting after acute intervention with tPA, mechanical thrombectomy or a combination of therapies The second group of AIS patients is critically ill as a result of their stroke, regardless of having or not having received an acute intervention In this section, our discussion will focus on practical hemodynamic, cardiac and hyperosmolar therapy principles related to admitting an AIS patient to the critical care unit

Hemodynamics

First published in 1955 and then approved for use within three hours in 1996, intravenous (IV)-tPA is the only AIS therapy with randomized controlled trial data demonstrating improve outcomes [2] In 2008, Hacke et al [3] demonstrated that certain patients can receive IV-tPA within an extended window of time up to 4.5 hours As a result of growing adoption of AHA guidelines and improved education of both patients and health care providers, more patients with AIS are being treated with IV-tPA The most feared side effect of IV-tPA is intracranial bleeding Per the AHA guidelines [1], patients that receive IV-tPA should have a systolic blood less than 180/105 mmHg for up to 24 hours after receiving IV-tPA Otherwise, AIS patients who were not exposed to an acute intervention should be allowed permissive hypertension up to a systolic blood pressure of 220mmg or diastolic blood pressure of 120mmHg.Depending on the clinical context, the recommendation is to use labetalol as needed (PRN) and/or nicardipine infusion to keep the patient’s systolic blood pressure below the desired limit Correct use of these agents depends on understanding the patient’s baseline level of hypertension and volume status on admission

AIS can acutely elevate blood pressure and patients who do not demonstrate this acute elevation may suffer from Chronic Heart Failure (CHF) or sympathetic stunned myocardium Actively lowering systolic blood pressure after acute stroke intervention can reduce the risk of intracerebral hemorrhage However, it may also place the remaining organ systems at risk for ischemia due to the patient’s chronic adaptation towards higher perfusion pressures In addition to blood pressure management, the patient’s volume status on admission is also an important clinical parameter to determine The goal for AIS patients is euvolemia [1], but realistically most patients are hypovolemicupon admission Therefore, AIS patients should receive IV isotonic fluids (i.e normal saline) unless the patient has risk factors that would lead to volume overload and pulmonary edema Anticipating volume overload is important because pulmonary edema can increase work of breathing, which could influence an AIS patient to evolve from respiratory insufficiency to acute respiratory failure

If an AIS patient can tolerate IV fluids, they should remain on maintenance fluids for a few days

The use of isotonic fluids that include dextrose should be avoided due to negative impact hyperglycemia (blood glucose > 200) has

on stroke outcomes First, even if a patient has been cleared for oral intake, the likelihood of patients consuming enough fluids to remain euvolemic is low and supporting perfusion of the cerebral penumbra is a key aspect of managing AIS patients in the ICU Secondly, time and further study is required to completely understand the patient’s cerebrovascular injury If evidence suggests contribution from collateral flow is preventing further ischemia or a critical arterial stenosis is related to stroke etiology, poor intravascular volume could lead to further ischemia There are cases where induced hypertension may be beneficial; therefore euvolemia is essential for proper vasopressor administration

Cardiac Complications

The current AHA/ASA guidelines recommend a baseline electrocardiogram and troponin assessment on initial evaluation of patients with AIS These studies should not delay reperfusion strategies, but are very important on admission for both diagnosing the potential stroke etiology as well as management of the patient Cardiac ischemia and arrhythmias after AIS are a very real complication of AIS and