Oxford Handbook of Critical Care - part 4 pps

Signifi cantl y worse haemodynamic effects have been reported with bicarbonate compared to equimolar sal ine in patients wi th severe heart fai lure.. Side-effects Sei zures fl umazenil,

P.180

Notes

Isotonic (1.26%) sodi um bicarbonate may be used to correct acidosi s associated wi th renal fai lure or to i nduce a

forced al kal ine di uresi s The hypertonic (8.4%) sol uti on is rarel y required i n i ntensive care practi ce to rai se bl ood pH

in severe metaboli c acidosi s Bi carbonate therapy is inappropriate when ti ssue hypoperfusion or necrosi s i s present

Administration may be i ndi cated as either speci fi c therapy (e.g alkali ne diuresis for sali cyl ate overdose) or i f the

patient i s symptomati c (usual ly dyspnoeic) i n the absence of ti ssue hypoperfusion (e.g renal fai lure)

The PaCO2 may rise if mi nute volume is not increased Bicarbonate cannot cross the cel l membrane wi thout

dissociation so the increase in PaCO2 may result in intracellular acidosi s and depression of myocardi al cell functi on

The decrease in pl asma i oni sed calci um may al so cause a decrease i n myocardi al contractil ity Signifi cantl y worse

haemodynamic effects have been reported with bicarbonate compared to equimolar sal ine in patients wi th severe

heart fai lure

Convincing human evidence that bi carbonate improves myocardi al contracti li ty or increases responsiveness to

ci rculating catechol ami nes i n severe aci dosis is lacking, though anecdotal success has been reported Aci dosis

rel ating to myocardi al depression i s rel ated to intracellular changes that are not accurately reflected by arterial blood

chemistry

Excessive administration may cause hyperosmol ali ty, hypernatraemi a, hypokal aemia and sodium overl oad

Bi carbonate may decrease ti ssue oxygen avai labil ity by a left shift of the oxyhaemogl obi n dissoci ation curve

Sodium bi carbonate does have a pl ace in the management of aci d retenti on or alkali loss, e.g chroni c renal fai lure,

renal tubul ar aci dosis, fi stulae, diarrhoea Fl ui d and/or potassi um deficits shoul d be corrected first

Ion content of sodium bicarbonate (mmol/l)

1.26% sodium bicarbonate 150 150 8.4% sodium bicarbonate 1000 1000

See also:

Bl ood gas analysis, p100; El ectrolytes

), p146; Crystal loids, p176; Cardi ac arrest, p272; Metaboli c aci dosis, p434; Sal icylate poi soning, p454

Routes

IV

Side-effects

Small er vol umes of coll oid are required for resuscitati on with l ess contributi on to oedema Mai ntenance of plasma

col loid osmoti c pressure (COP) i s a useful effect not seen wi th crystall oi ds, but coll oids contain no cl otting factors or

other plasma enzyme systems

Al bumin is the main provider of COP and has several other roles There i s no evidence that mai ntaining pl asma

albumi n l evels, as opposed to plasma COP wi th artifici al pl asma substitutes, is better

Al bumin 20–25% and Pentaspan 10% are hyperoncotic and used to provi de col loi d where salt restricti on i s necessary

Thi s i s rarely necessary i n i ntensi ve care as plasma vol ume expansion i s related to the weight of coll oi d i nfused

rather than the concentration Arti fi cial coll oi ds used wi th ul trafil trati on or diuresis are just as effective in oedema

states

Pol ygeline i s a 3.5% sol uti on contai ni ng cal cium (6.25mmol/l ) Thi s prevents use of the same giving set for blood

transfusions Succinyl ated gelatin is a 4% soluti on with a larger molecul ar size than polygeli ne giving a sl ightly

longer effect Thi s, and the l ack of cal ci um in sol uti on, make it more useful than polygel ine for short term pl asma

vol ume expansion

In patients with capi ll ary leak albumi n and smaller molecul ar wei ght coll oids l eak to the i nterstiti um In these cases

it is perhaps better to use l arger mol ecular weight coll oi ds such as hydroxyethyl starch, though conclusive evidence

is lacki ng

Hetastarch and hexastarch are usuall y 6% soluti ons with a hi gh degree of protecti on from metabol ism due to a high

degree of substituti on (proporti on of glucose units substituted with hydroxyethyl groups—DS) or a high rati o of C2 to

C6 carbon atoms substituted (C2:C6 rati o) The molecular weight ranges vary but mol ecular sizes are large enough to

ensure a prolonged effect These are the most useful colloids i n capi llary leak Prolonged itchi ng related to

intradermal depositi on and interference with coagulation are complicati ons i f excessi ve doses are used

Pentastarch and tetrastarch provide only a short term effect si mi lar to succi nyl ated gelati n

Unique features of albumin

Transport of various mol ecules

Free radical scavengi ng

Binding of toxi ns

Inhibi tion of platelet aggregation

Relative persistence of colloid effect

Hetastarch (high MW, high DS, low C2:C6 ratio) ++++

Hexastarch (medium MW, high DS, high C2:C6 ratio) ++++

Pentastarch (medium MW, low DS, low C2:C6 ratio) ++

Tetrastarch (low MW, low DS, high C2:C6 ratio) ++

Persistence is dependent on mol ecular size and protection from metabol ism

High DS and high C2:C6 ratio protect hydroxyethyl starch from metaboli sm

All arti ficial coll oids are pol ydi sperse (i e there is a range of molecul ar si zes)

Crystall oids, p176; Blood transfusi on, p182; Blood products, p252; Basic resuscitati on, p270; Flui d chal lenge, p274;

Di abetic ketoacidosi s, p442; Systemi c i nfl ammati on/mul tiorgan fail ure, p484; Sepsis and septi c shock treatment,

p550; Anaphylactoi d reacti ons, p496; Burns—fl uid management, p510; Post-operative i ntensi ve care, p534

Blood transfusion

Blood storage

Bl ood cel ls are eventual ly destroyed due to oxidant damage duri ng storage of whole bl ood Since white cell s and

plasma enzyme systems are of importance in thi s cel lul ar destruction, effects are correspondingly less severe for

packed red cell s Bl ood used for transfusion in most of Europe is now routi nel y l eukodepleted Microaggregate

formation is associated with platel ets, white cell s and fibri n and range i n size from 20–170µm The risk of

microaggregate damage is reduced with packed red cells In addi ti on to spherocytosi s and haemolysis, prolonged

storage depl etes ATP and 2,3-DPG levels thus increasi ng the oxygen affinity of the red cel ls If whole bl ood is to be

used i n cri ticall y i ll patients i t should be as fresh as possible

Compatibility

In an emergency, wi th massi ve blood l oss that threatens l ife, i t i s permissible to transfuse O negati ve packed cel ls

but a sample must be taken for groupi ng prior to transfusion With modern l aboratory procedures it is possi bl e to

obtain ABO compatibi li ty for group speci fic transfusion wi thi n 5–10mi n and a full cross-match in 30min

Hazards of blood transfusion

Citrate toxi city—hypocal caemia is rarel y a probl em and the prophyl actic use of calci um suppl ementation i s notrecommended

Potassi um load—potassium returns to cel ls rapidly but hyperkal aemi a may be a problem if bl ood is stored atroom temperature

Sodium load—from ci trate if the transfusion i s massive

Hypothermi a—can be avoided by warmi ng bl ood as it is transfused

Jaundice—haemolysis of incompatibl e or old bl ood

Pyrexia—i mmunologi cal transfusion reactions to i ncompati ble red or white cell s or platelets

DIC—parti al activation of clotti ng factors and destructi on of stored cells, either in ol d blood or when transfusi on

is incompati ble

Anaphyl actoi d reaction—urticaria is common and probably due to a reaction to transfused pl asma proteins; ifsevere it may be treated by slowing the transfusi on and gi ving chlorpheni ramine 10mg IV/IM In severeanaphyl axi s, in addition to standard treatment, the transfusion shoul d be stopped and saved for l ater anal ysi sand a sample taken for further cross-matchi ng

Transmission of di sease—including vi ruses, parasites (malaria), prions

Transfusi on-rel ated acute l ung injury (TRALI) and other i mmune reacti ons

A multicentre tri al suggested li beral transfusion in the criticall y i ll produced less favourabl e outcomes,particularl y i n younger, l ess si ck patients, than usi ng a tri gger haemoglobin of 7g/dl

Key trial

Hebert PC, Well s G, Blajchman MA et al, for the Tranfusion Requi rements in Cri tical Care Investi gators A

mul ti center, randomi zed, control led cl inical tri al of transfusi on requirements i n critical care N Engl J Med 1999;

340:409–17

See also:

Cal cium, magnesium and phosphate, p148; Ful l blood count, p154; Coagulati on moni toring, p156; Basi c resuscitation,

p270; Haemothorax, p302; Haemoptysis, p304; Upper gastrointesti nal haemorrhage, p344; Bleedi ng varices, p346;

Lower intestinal bleedi ng and colitis, p348; Bleedi ng disorders, p396; Anaemia, p400; Haemol ysi s, p404; Mal ari a,

p490; Anaphylactoi d reacti ons, p496; Post-operati ve intensive care, p534; Post-partum haemorrhage, p542

Ovid: Oxford Handbook of Critical Care

Editors: Singer, Mervyn; Webb, Andrew R.

Title: Oxford Handbook of Critical Care, 2nd Edition

Copyri ght ©1997,2005 M Si nger and A R Webb, 1997, 2005 Publ ished in the United States by Oxford Universi ty

IV (sal butamol, epi nephrine, terbutali ne, ipratropium, aminophyll ine, hydrocortisone, ketami ne)

PO (ami nophyl li ne, predni solone)

Side-effects

CNS stimulation (salbutamol , epinephrine, terbutal ine, aminophyll ine)Tachycardia (sal butamol, epi nephrine, terbutaline, ami nophyl li ne, ketami ne)Hypotensi on (sal butamol, terbutal ine, aminophyll ine, i soflurane, halothane)Hypergl ycaemi a (sal butamol, epi nephri ne, terbutaline, hydrocortisone, prednisolone)Hypokal aemia (salbutamol, epinephrine, terbutali ne, hydrocortisone, prednisolone)Lactic acidosi s (sal butamol )—rare

Notes

Sel ective β2 agoni sts are usuall y gi ven by inhal ati on via a pressuri sed aerosol or a nebul izer Inhal ati on often gives

rapid relief of bronchospasm, although the aerosol is of less benefit in severe asthma

Nebuli zed drugs require a minimum volume of 4ml and a dri ving gas flow of 6–8l/min

In extremis, epinephrine may be used IV, SC or i njected down the endotracheal tube As epinephri ne is not selective,

arrhythmi as are more li kel y However, the α agoni st effect may reduce mucosal swel ling by vasoconstriction

Ipratropium bromi de has no systemic effects and does not depress mucocil li ary cl earance It is synergistic wi th β2

agonists but has a sl ower onset of acti on

Ami nophyl li ne is synergistic wi th β2 agonists Dosages must be adjusted accordi ng to plasma level s (range

10–20mg/l ) since toxi c effects may be severe Dose requirements are reduced by heart fai lure, liver di sease, chronic

airfl ow l imitation, fever, ci metidi ne, erythromyci n Dose requirements are i ncreased in chi ldren, smokers and those

with a moderate to hi gh alcohol i ntake

See also:

Steroids, p262; Chronic airflow l imi tation, p286; Asthma—general management, p296; Asthma—ventilatory

management, p298

Drug dosages

Acute respiratory fai lure due to fai lure of ventilatory dri ve.

Drug i nduced venti latory failure, e.g as a result of excessive sedation or post-operatively

Routes

IV

Modes of action

Nal oxone—short acti ng opi ate antagoni st

Flumazenil —short acti ng benzodiazepi ne antagonist

Doxapram—general ised central nervous system stimulant with predomi nant respiratory sti mul ati on at lowerdoses Stimulation of carotid chemoreceptors at very l ow doses with i ncreased tidal vol umes

Almitrine—i ncreases the sensi ti vity of carotid chemoreceptors to hypoxaemi a and hypercapnia

Side-effects

Sei zures (fl umazenil, doxapram)Tachyarrhythmias (nal oxone, flumazeni l)Hal lucinations (doxapram)

Notes

Respiratory stimulants are mainl y used in patients wi th chroni c airflow l imi tation who devel op acute hypercapnic

respi ratory failure Effects of doxapram are short-li ved so infusi on is necessary After about 12h infusion the effects

on ventil atory dri ve are reduced

Nal oxone may be used i n respiratory depression due to opi ate drugs Since i t reverses all opi ate effects, it may be

better to reverse respi ratory depressi on with non-specific respi ratory stimulants, l eavi ng pai n rel ief intact It may

need to be repeated when long acti ng opi ates are involved

P.190

As most benzodi azepi nes are l ong acting compared to fl umazenil , repeated doses may be necessary

Al mitrine does not produce central respi ratory stimulation but i t does i mprove ventil ation–perfusion matching by

augmenting hypoxic pulmonary vasoconstriction Effects continue for several hours after i njecti on

Drug dosages

Naloxone 0.1–0.4mg Flumazenil 0.2mg over 15min (0.1mg/min to max 2mg)

Almitrine 0.25–0.5mg/kg over 30min

Key paper

Greenstone M, Lasserson TJ Doxapram for venti latory fail ure due to exacerbati ons of chroni c obstructi ve pul monary

disease Cochrane Database Syst Rev 2003; CD000223 Review

See also:

Opi oi d anal gesics, p234; Sedati ves, p238; Respiratory fail ure, p282; Sedative poisoni ng, p458; Post-operati ve

intensive care, p534

Nitric oxide

Nitri c oxide i s now recognised as a fundamental mediator in many physiol ogi cal processes One of its most i mportant

effects i s smooth muscle relaxati on; ni tric oxi de is the major local controll er of vascul ar tone via effects on cycl ic

GMP

Inhaled nitric oxide

Nitri c oxide i s provided for inhalati on from cyli nders (1000ppm nitric oxide in ni trogen) It is di luted with i nspiratory

gases, ei ther at the gas suppl y to the ventil ator or i n the inspi ratory li mb of the venti lator circuit, to provi de an

inhal ed concentration of 1–40ppm, al though most patients requi re less than 20ppm Inhal ation produces

vasodi latati on at the si te of gas exchange, and may improve venti lation–perfusi on matchi ng and reduce pulmonary

artery pressures Randomised multi-centre studi es in patients with acute l ung i njury have revealed no long-term

benefi t or outcome improvement

Side-effects

Nitri c oxide i s i mmediatel y bound to haemoglobi n ensuring l ocal effects only There is no tolerance but patients can

become dependent on conti nued i nhalation wi th rebound pul monary hypertension and hypoxaemia on withdrawal For

thi s reason, wi thdrawal must be gradual Excessi ve humidi fi cation of inspi red gases may form ni tri c acid wi th NO; the

use of heat–moi sture exchangers rather than water baths i s recommended

Monitoring

Nitri c oxide and nitrogen dioxide concentrations may be moni tored convenientl y wi th portable fuel cel l anal ysers or

by chemil umi nescence It i s i mportant to monitor concentrations of both gases in the i nspiratory limb of the

ventil ator circui t Monitori ng of nitrogen dioxide i s i mportant to ensure that toxic doses are not formed with the

oxygen in the i nspired gas and subsequentl y i nhaled by the pati ent Although i t i s extremely rare to see toxic

nitrogen di oxi de concentrations (>5ppm) it is possibl e to remove nitrogen dioxide from the inspi red gas by usi ng a

soda l ime adsorber Methaemogl obi n i s formed when ni tric oxi de binds to haemogl obin Prolonged i nhalation at hi gher

doses may rarel y produce si gni fi cant methaemoglobinaemia (>5%) and thi s should therefore be monitored dail y

Achieving the correct dose

Approximatel y 50% of patients with severe respiratory fai lure respond to ni tric oxi de However, the most effective

dose vari es It is usual to start at 1ppm for 10min and moni tor the change in PaO2/FIO2 rati o An increase shoul d be

fol lowed by an i ncrease in nitri c oxide concentration to 5ppm for a further 10min Thereafter, the dose i s adjusted

according to response at 10min i ntervals until the most effective dose i s found Si nce the underlying pathophysiology

may change, i t is important to assess the dose response at dail y i ntervals, ai mi ng to keep the dose at the lowest

effective level

Scavenging

Si nce the concentrations used are so smal l, dil uti on of exhaled gases i nto the atmosphere is unlikely to produce

important environmental concentrati ons In the air-condi ti oned intensi ve care environment ai r changes are so

Del li nger RP et al , for the Inhal ed Nitri c Oxide i n ARDS Study Group Effects of inhal ed nitri c oxide i n pati ents with

acute respi ratory di stress syndrome: results of a randomized phase II trial Cri t Care Med 1998; 26:15–23

Lundi n S et al , for the The European Study Group of Inhal ed Nitri c Oxide Inhalation of ni tric oxi de in acute lung

injury: results of a European mul ticentre study Intensi ve Care Med 1999; 25:911–19

See also:

Vasodi lators, p198; Acute respiratory distress syndrome (1), p292; Acute respi ratory di stress syndrome (2), p294

Surfactant

In ARDS there i s decreased surfactant production, biochemical abnormal ity of the surfactant produced and inhi bition

of surfactant function The net result is al veol ar and small ai rway col lapse Surfactant also contri butes to host

defence agai nst mi cro-organisms Surfactant replacement woul d be expected to exert therapeuti c effects on lung

mechanics, gas exchange and host defence

Insti llati on of surfactant (either as a l iquid or nebul ised) via the endotracheal tube into the lungs i s associated wi th

improved outcome i n neonatal respiratory distress syndrome Potential i ndi cations in adults incl ude ARDS,

pneumonia, chronic ai rflow li mitati on and asthma Mul tiple studi es i n ARDS have yet to demonstrate mortality

benefi t, though this may be related to the type of surfactant, the vol ume used, or the deli very system

Studi es have demonstrated i mproved oxygenation wi th recombinant surfactant protei n C and a trend to improved

survi val in patients wi th direct l ung injury Further studies are underway using recombi nant surfactant protein C with

phospholi pi ds, and wi th surfactant protei ns B and C The surfactant is insti lled i nto the l ungs via an endotracheal

catheter

Compli cations of surfactant treatment have included increased cough, sputum production, bronchospasm, increasd

peak airway pressure and adverse effects on pulmonary function These can be minimi sed by adequate sedation and

neuromuscul ar blockade before insti lli ng surfactant

Key trial

Spragg RG, Lewi s JF, Wal mrath HD et al Effect of recombinant surfactant protein C-based surfactant on the acute

respi ratory di stress syndrome N Engl J Med 2004; 351:884–92

See also:

Acute respi ratory di stress syndrome (1), p292; Acute respiratory distress syndrome (2), p294

Ovid: Oxford Handbook of Critical Care

Editors: Singer, Mervyn; Webb, Andrew R.

Title: Oxford Handbook of Critical Care, 2nd Edition

Copyri ght ©1997,2005 M Si nger and A R Webb, 1997, 2005 Publ ished in the United States by Oxford Universi tyPress Inc

> Table of Co ntents > Car dio vasc ular Dru gs

Modes of action

Increase force of myocardial contraction, either by stimulating cardiac β1 adrenoreceptors (catecholamines),decreasing cAMP breakdown (PDE inhibi tors), i ncreasing calci um sensi tivity (Ca sensiti sers), di rectl y i ncreasingcontracti li ty (di goxi n), or inhi biting neuronal reuptake of noradrenali ne (dopexamine) Al l agents except di goxin

The increase in cardi ac work i s partial ly offset in those drugs possessing associated dil ator effects.

Other than epinephrine (when used for its vasoconstrictor effect i n cardiopulmonary resuscitati on) or di goxin (forlong term use i n chronic heart failure), i notropes are usual ly gi ven by continuous IV i nfusi on titrated for effect

Anginal chest pain, or ST-segment and T-wave changes on ECG

Notes

Epi nephrine, norepinephrine, dobutamine and dopamine should be given via a central vein as ti ssue necrosi s may

occur secondary to peri pheral extravasati on

Drug dosages

Epinephrine Infusion starting from 0.05µg/kg/min Norepinephrine Infusion starting from 0.05µg/kg/min Dobutamine Infusion from 2.5–25µg/kg/min

Dopamine Infusion from 2.5–50µg/kg/min Dopexamine Infusion from 0.5–6µg/kg/min

Milrinone Loading dose of 50µg/kg over 10min followed by infusion from

0.375–0.75µg/kg/min

Enoximone Loading dose of 0.5–1mg/kg over 10min followed by infusion from

5–20µg/kg/min

Digoxin 0.5mg given PO or IV over 10–20min Repeat at 4–8h intervals until loading

achieved (assessed by clinical response) Maintenance dose thereafter is 0.0625–0.25mg/day depending on plasma levels and clinical response.

Levosimendan 12–24µg/kg over 10min followed by 0.1µg/kg/min for 24h

See also:

Intra-aorti c ball oon counterpulsati on, p58; Cardiac output—thermodiluti on, p122; Cardiac output—other invasi ve,

p124; Cardiac output—non-invasive (1), p126; Cardiac output— non-invasive (2), p128; Basic resuscitati on, p270;

Cardiac arrest, p272; Fl uid chall enge, p274; Hypotensi on, p312; Sepsis and septic shock—treatment, p486; Care of

the potential organ donor, p552

Vasodilators

Types

Nitrates: e.g glyceryl tri ni trate, isosorbi de di nitrateAngiotensin converting enzyme (ACE) i nhi bi tors: e.g captoprilSmooth muscl e relaxants: e.g sodi um nitroprussi de, hydralazineα-adrenergic antagoni sts: e.g phentolamine

β2-adrenergi c agoni sts: e.g salbutamolCalcium antagoni sts: e.g ni fedipi ne, di ltiazemDopaminergic agoni sts: e.g dopexamine

Phosphodiesterase i nhibi tors: e.g enoximone, mil ri none, sil denafi lProstaglandi ns: e.g epoprostenol (PGI2), al prostadi l (PGE1)

B-type natri uretic pepti de analogues, e.g nesiritide

Modes of action

Increase cyclic GMP concentration (by nitric oxi de donati on or by inhibiti ng cGMP breakdown), or acts directly ondopaminergic receptors l eading to vasodilatation

Reduce (to varyi ng degrees) ventri cul ar preload and/or afterl oad

Reduce cardiac work

Side-effects/complications

Hypotensi on (often associ ated with concurrent hypovolaemia)Tachycardia (often associ ated with concurrent hypovolaemia)Symptoms i nclude headache, flushi ng, postural hypotensionRenal fail ure (ACE inhibi tors)—especial ly with renal artery stenosis, hypovol aemi a, non-steroidals

Notes

Gl yceryl trini trate and i sosorbide di nitrate reduce both preload and afterload At hi gher dose the afterload effect

becomes more promi nent

Tol erance to ni trates usually commences wi thin 24–36h unless i ntermi ttent oral dosing is used Progressive increases

in dose are required to achieve the same effect

Prolonged (>24–36h) dose-rel ated admi nistrati on of sodi um ni troprussi de can rarel y produce a metabolic acidosi s

rel ated to cyanide accumulati on

ACE inhi bitor tablets can be crushed and given either SL or vi a a nasogastric tube

Dopami nergi c drugs i mprove splanchnic bl ood flow though cli ni cal benefi ts are unproved

Hydral azi ne has an unpredictable effect on bl ood pressure and, if given IV, shoul d be used wi th caution

Drug dosages

Nitrates Glyceryl trinitrate 2–40mg/h

Isosorbide dinitrate 2–40mg/h

Sodium nitroprusside 20–400µg/min

Hydralazine 5–10mg by slow IV bolus, repeat after 20–30min Alternatively, by infusion

starting at 200–300µg/min and reducing to 50–150µg/min

ACE inhibitors Captopril: 6.25mg test dose increasing to 25mg tds

Enalapril: 2.5mg test dose increasing to 40mg od Lisinopril: 2.5mg test dose increasing to 40mg od

Nifedipine: 5–20mg PO Capsule fluid can be injected down nasogastric tube or given

sublingually Phentolamine 2–5mg IV slow bolus Repeat as necessary.

Dopexamine Infusion from 0.5–6µg/kg/min

Milrinone Loading dose of 50µg/kg over 10min followed by infusion from

0.375–0.75µg/kg/min

Enoximone Loading dose of 0.5–1mg/kg over 10min followed by infusion from

5–20µg/kg/min

Epoprostenol, alprostadil Infusion from 2–30ng/kg/min Nitric oxide By inhalation: 2–40ppm

Nesiritide 2µg/kg bolus followed by infusion of 0.01–0.03µg/kg/min

See also:

Bl ood pressure monitori ng, p110; Cardiac output—thermodil uti on, p122; Cardiac output—other invasi ve, p124;

Cardiac output—non-invasive (1), p126; Cardiac output—non-invasi ve (2), p128; Hypotensive agents, p202;

Antiangi nal agents, p208; Nitric oxi de, p190; Basic resuscitati on, p270; Flui d chal lenge, p274; Hypertension, p314;

Acute coronary syndrome (1), p320; Acute coronary syndrome (2), p322; Heart fail ure—assessment, p324; Heart

fai lure—management, p326; Pre-eclampsia and eclampsi a, p538

Vasopressors

Types

α-adrenergic: e.g norepi nephri ne, epinephrine, dopami ne, ephedrine, phenylephrine, methoxamineDrugs reduci ng producti on of cycl ic GMP (i n septic shock): e.g methylthionini um chloride (methylene blue)Vasopressin or synthetic analogues, e.g terl ipressin

Increased myocardi al irritabi lity, especi al ly with concurrent hypovolaemi a, leading to arrhythmias andtachycardia

Decreased peripheral perfusion and distal ischaemi a/necrosi s

Notes

Pressor agents shoul d be avoided, if possi ble, i n l ow cardi ac output states as they may further compromise the

ci rculation

Methoxami ne and phenyl ephri ne are the ‘purest’ pressor agents; other α-adrenergic agents have inotropi c properties

to greater or l esser degrees Ephedrine i s simi lar to epinephrine but its effects are more prolonged as it is not

metabolised by monoami ne oxi dase

Effects of pressor agents on splanchnic, renal and cerebral ci rculations are variable and unpredi ctable

Pul monary vascular resi stance is al so rai sed by these agents

Methyl thi oni ni um chl ori de (methylene blue) i nhi bits the NO–cGMP pathway It i s currently unl icensed as a pressor

agent and its use has only been reported i n a few small case series A multicentre study of a NO synthase inhibitor

(L-NMMA) was prematurely di sconti nued due to adverse outcomes

Vasopressin (short half-li fe, infusion needed) and terli pressi n (longer half-life, can be gi ven by bol us) may be

effective in treating catechol ami ne-resistant vasodil atory shock Paradoxi cal ly, such patients respond to smal l doses

that have no pressor effect in healthy people Multi centre outcome studi es are ongoi ng

Excessive dosing of any pressor agent may l ead to regional ischaemi a, e.g cardiac, spl anchni c Digital ischaemia

may respond to prompt administration of intravenous prostanoids (e.g PGE1, PGI2)

Drug dosages

Lopez A, et al Mul ti ple-center, randomized, placebo-control led, double-bli nd study of the ni tri c oxi de synthase

i nhibi tor 546C88: effect on survival in patients wi th septic shock Crit Care Med 2004; 32:21–30

Landry DW, et al Vasopressin defici ency contri butes to the vasodi lation of septi c shock Ci rculation 1997;

95:1122–5

Hypotensive agents

Types

Vasodi latorsα- and β-adrenergic bl ockers

In routine ICU practi ce β-blockers are used relatively infrequentl y because most have a long half-li fe and thenegati ve i notropic effects are generall y undesirabl e Exceptions are esmolol and labetalol , both of whi ch haveshort hal f-l ives and vasodil ating properti es

Side-effects/complications

Excessive hypotensi onHeart fail ure (with β-blockers)Peri pheral hypoperfusion (wi th β-blockers)Bronchospasm (wi th β-blockers)

Decreased sympathetic response to hypogl ycaemi a (with β-bl ockers)

Notes

In criti cal ly il l pati ents i t is often advi sable to use short-acti ng β-bl ockers by i nfusion

Drug dosages

Nitrates Glyceryl trinitrate 2–40mg/h

Isosorbide dinitrate 2–40mg/h

Sodium nitroprusside 20–400µg/min.

ACE inhibitors Captopril: 6.25mg test dose increasing to 25mg tds

Enalapril: 2.5mg test dose increasing to 40mg o.d Lisinopril: 2.5 mg test dose increasing to 40mg o.d

Nifedipine: 5–20mg PO Capsule fluid can be injected down nasogastric tube or given

sublingually.

Phentolamine 2–5mg IV slow bolus Repeat as necessary

Esmolol A titrated loading dose regimen is commenced followed by an infusion rate of

50–200µg/kg/min.

Propranolol Initially given as slow IV 1mg boluses repeated at 2min intervals until effect is

seen (to maximum 5mg)

Hydralazine 5–10mg by slow IV bolus, repeat after 20–30min Alternatively, by infusion

starting at 200–300µg/min and reducing to 50–150µg/min.

See also:

Bl ood pressure monitori ng, p110; Cardiac output—thermodil uti on, p122; Cardiac output—other invasi ve, p124;

Cardiac output—non-invasive (1), p126; Cardiac output—non-invasi ve (2), p128; Vasodil ators, p198; Basic

resuscitati on, p270; Flui d challenge, p274; Hypertensi on, p314; Pre-eclampsi a and ecl ampsia, p538

Antiarrhythmics

Onl y anti arrhythmics li kel y to be used in the ICU setting are descri bed

For supraventri cular tachyarrhythmi as:

adenosi ne, verapami l, ami odarone, digoxi n, β-blockers, magnesiumFor ventricular tachyarrhythmias:

amiodarone, l idocai ne, fl ecainide, bretyli um, β-blockers, magnesium

Al l anti arrhythmi c agents have side-effects; other than digoxi n they are negatively inotropi c to greater or lesser

degrees and may induce profound hypotension (e.g verapamil , β-bl ockers) or bradycardia (e.g β-bl ockers,

ami odarone, digoxi n, lidocaine) β-blockers i n particular should be used with cauti on because of these effects

Al l A-V blockers are contrai ndi cated in re-entry tachycardia (e.g Wol ff–Parkinson–Whi te syndrome)

Adenosine: very short-acting; may revert paroxysmal SVT to si nus rhythm Ineffecti ve for atrial flutter andfibril lation, VT Contraindicated i n 2° and 3° heart block, si ck si nus syndrome, asthma May cause fl ushing,bronchospasm and occasional severe bradycardi a