JOURNAL OF SCIENCE, Hue University, N 0 61, 2010 EVALUATE THE EFFECTS OF KETAMINE PAIN RELIEF DRUG IN PREHOSPITAL TRAUMA CARE A CONTROLLED CLINICAL TRIAL IN QUANG TRI, VIETNAM Tran Ki
Trang 1JOURNAL OF SCIENCE, Hue University, N 0 61, 2010
EVALUATE THE EFFECTS OF KETAMINE (PAIN RELIEF DRUG) IN
PREHOSPITAL TRAUMA CARE
A CONTROLLED CLINICAL TRIAL IN QUANG TRI, VIETNAM
Tran Kim Phung Quang Tri Health Services
SUMMARY
To compare the analgesic effect and adverse events (nausea/vomiting) of Ketamine
versus Morphine analgesia to injury patients during pre-hospital evacuations Methods:
Patients injured in one sector get Ketamine relief (treatment group) Patients from the other sector get Morphine (controlled group) Patient’s actual pain was assessed and rated on VAS The difference VAS1-VAS2 is the indicator of analgesic effect Adverse effect (nausea/vomiting)
based on clinical assessment at the end point and interview Results: 257 patients included of
which: 140 in Ketamine and 117 in Morphine was analysed Significant difference between VAS1-VAS2, p<0.0001 No significant difference of analgesic effect between Ketamine and Morphine group, p>0.05 Analgesic effect of Ketamine is very clear in every ISS level,
regardless of male, female and age groups Conclusions: Analgesic effect of Ketamine in
trauma care at community is clear, the same analgesic effect of Morphine Adverse effect (nausea/vomiting) is much lower in Ketamine than Morphine
Key words: Analgesic effect, adverse events, pre - hospital.
1 Introduction
Efficient pain relief is crucial in primary life support for trauma victims Acute pain makes breathing efforts inefficient and thereby adversely affects oxygenation Persistent pain and anxiety also trigger post injury release of catecholamines and cortisol and thus accelerate a post-injury stress response and aggravate immunosuppression Uncontrolled post-injury stress response is a heavy risk factor for trauma death
In most pre - hospital trauma systems, opioid analgesics have been the analgesics of choice for the last few decades These are potent analgesics, however they are not without potentially fatal side - effects Evacuations are often rough and difficult
in rural trauma scenarios; there may be mass casualties; patients may be carried off-road without ambulances; and the first helpers may not be able to provide continuous close
Trang 2care and monitoring of vital signs in - field Opioid analgesics may under such circumstances cause vomiting with risk of airway obstruction, especially so in patients weak from blood loss and hypotension Airway block due to aspiration of vomit in un/low-conscious patients is considered the most common reason for avoidable trauma death Also the range of therapeutic doses is narrow in opioids There is thus a risk that accidental over-dosage causes respiratory depression, hypotension and loss of protective airway reflexes
Ketamine hydrochloride is a non-opioid potent analgesic that has been used for anaesthesia for decades Ketamine stimulates the sympathetic nervous system and causes moderate increases in the heart rate and systolic blood pressure, a side-effect considered positive in bleeding trauma victims Ketamine does not affect the respiration and laryngeal reflexes; under ketamine analgesia and anaesthesia the patient breathes spontaneously and maintains full airway control Thus the drug does not have the dangerous side-effects seen with opioids, even if administered accidentally in doses that are too high
In Vietnam, morphine is routinely used for pre - hospital trauma pain relief So far, Ketamine has not been used for trauma pain relief outside hospitals Setting up a systematic pre - hospital trauma system in the province of Quang Tri, we want to study the effect of ketamine analgesia in protracted evacuations
Objectives: This study compared the analgesic effect and adverse effects of ketamine and morphine in pre - hospital trauma care where medical resources were scarce
2 Methodology
Study population
Inclusion criteria
Any patient in Quang Tri Province that was injured during the study period, regardless of type of trauma, whose pre - hospital life support was provided by trained health workers The patients were given medical assistance during evacuation to Quang Tri Provincial Hospital (QT-PH), the end-point for this study
Exclusion criteria
Refusal of analgesia by patient or patient’s family
Deeply unconscious patients (no response to pain stimuli)
Patients who had already died on first medical contact in-field
Patients given general or local anaesthesia in-field for invasive life-support
Trang 3Patients with pre - hospital evacuation time < 10 minutes
Sampling and recruitment
A systematic cluster sampling technique was used in this study
We divided the province into two geographical sectors (“Sector 1” and “Sector 2”), each sector having approximately the same number of patients and approximately the same transport times
Patients injured in one sector received ketamine pain relief (Treatment Group); patients from the other sector (the rest of Quang Tri province) received morphine pain relief (Control Group) To reduce the impact of systematic failures, the sectors were then crossed over every month: Sector 1 shifts to Control, Sector 2 shifts to Treatment Both groups were stratified according to injury severity using the Injury Severity Score (ISS, 10): Moderate injuries = ISS <9 Serious injuries = ISS 9 – 15 Major injuries = ISS >15
Main variables
Analgesic effect:
Patient’s actual pain assessed and rated on the Visual Analogue Scale (VAS) by the trauma care provider at two points:
First (VAS1): at the first contact in-field immediately before life support starts Second (VAS2): immediately on admission at the provincial hospital
The difference (VAS1) – (VAS2) is the indicator of analgesic effect
VAS1 and VAS2 were rated each time by the same health worker Therefore, all patients were accompanied to the provincial hospital by the local health worker who started the in-field treatment
Adverse events:
Nausea and/or vomiting during the pre - hospital phase Categorical variable, Yes/No, based on clinical assessment at the end-point, plus information from the patient, patient’s family and pre - hospital care provider
The intervention
Ketamine treatment:
Intermittent intravenous dose(s) 0.2mg – 0.3mg/kg body weight The doses were repeated until satisfactory pain relief was achieved as assessed by the trauma paramedic Each dose was given slowly over more than 60 seconds
Control treatment:
Trang 4One intramuscular dose of morphine 10 mg (adults)
Sample size
2 2
/ 2
/
d
Z Z
p p
p1 = 0.20: nausea/vomit rate by morphine
p2 =0.01: nausea/vomit rate by ketamine
The study concluded when at least 125 consecutively injured patients were included in each group (treatment group and control group), the study ended 30 March
2009
Time schedule
The inclusion of patients started from 1 August 2007 to 1 July 2008
Creating data for statistical analyses
The statistical analysis was performed using JMP and PEST software The main outcome variables (analgesic effect and adverse effect on airways) were analysed by sequential statistics using double triangular tests
3 Results
During the study process, a total of 320 samples was collected Study included
257 samples Of which : Ketamine n=140, Morphine n=117
3.1 Matched pairs analysis by analgesia
Table 3.1 Matched pairs analysis by analgesia
Total n = 257 Ketamine n=140 Morphine n=117
Trang 5Total n = 257 Ketamine n=140 Morphine n=117
3.2 Matched pairs analysis by severity level for each analgesia group
Table 3.2 Matched pairs analysis by severity level for each analgesia group
Ketamine Morphine Ketamine Morphine Ketamine Morphine
Mean
Prob > |t| <.0001 <.0001 <0.0001 <0.0005 <.0001 <.0001 Test Across
Mean
3.3 Matched pairs analysis by Gender
Table 3.3 Matched pairs analysis by Gender
Trang 6GENDER MALE FEMALE
3.4 Nausea/vomitting
Table 3.4 Nausea/vomitting frequency of Ketamine and Morphine
3.5 Matched pairs analysis by age (<15)
Table 3.5 Matched pairs analysis by age (<15)
Mean
Trang 7AGE <15 Ketamine Morphine Male Female
Test Across
Mean
3.6 Matched pairs analysis by age (15-54)
Table 3.6 Matched pairs analysis by age (15-54)
Average
Degrees of
P value <.0001 <.0001 <.0001 <.0001 <.0001 Test among
3.7 Matched pairs analysis by age (>=55)
Table 3.7 Matched pairs analysis by age (>=55)
Trang 8AGE>=55 KETAMIN MORPHIN MALE FEMALE
Degrees of
P value <.0001 <.0001 <.0001 <.0001 <.0001
4 Discussion
4.1.Matched pairs analysis by analgesia
In our results there was a statistically significant difference between VAS1 and VAS2 for the total sample, as well as the individual groups: ketamine and morphine p<0.0001 The mMean difference for the ketamine group was found to be 3.44, which that was slightly higher than the morphine group (3.11), however, no signifcant difference was found between the mean difference of the two groups P = 0.1679
It also means that: the analgesic effect of ketamine is the same as the analgesic effect of morphine
4.2 Matched pairs analysis by ISS level for each analgesia group
In the ketamine group, the diference between VAS1 and VAS2 were 3.35, 3.12 and 3.66, slightly higher in comparison to 3.11, 2.65, 3.27 in the morphine group, respectively But there was no significant difference in analgesia across each ISS group p>0.05
4.3 Matched pairs analysis by gender
There was a significant difference between VAS1 and VAS2 in male and female groups, p<0.001 but no significant difference between male and female p>0.005
It also means that: the analgesic effect of ketamine and morphine is the same with male and female patients
4.4 Nausea/vomitting
In the ketamine group (n= 140) there were 7 cases of nausea, a rate of 5%; 3
Trang 9of nausea, a rate of 30,77%; 32 cases of vomitng, a rate of 27, 35%
It showed that a higher rate of nausea/vomiting was found in morphine group compared to the ketamine group
4.5 Matched pairs analysis by age of 6-14
In the ketamine group, there were 14 children, who were injured patients with an age range of 6-14 years In the morphine group, there were 14 children- injured patients with an age range of 6-14 years (4 females)
There was a significant difference between VAS1 and VAS2 in the ketamine and morphine groups, p<0.001 and 0.0045 respectively, but no signifcant difference was found between the mean difference of the two groups p = 0.45
4.6 Matched pairs analysis by age of 15-54
In the ketamine group, there were 102 children- injured patients with an age range of 15-54 years In the morphine group, there were 85 children- injured patients with an age range of 15-54 years
There was a significant difference between VAS1 and VAS2 in the ketamine and morphine groups, p<0.001 and 0.0001 respectively, but no signifcant difference was found between the mean difference of the two groups p = 0.175
4.7 Matched pairs analysis by age of >=55
In the ketamine group, there were 24 children- injured patients with an age range
of >=55 years In the morphine group, there were 25 children- injured patients with an age range of >=55 years
There was a significant difference between VAS1 and VAS2 in the ketamine and morphine groups, p<0.0001 and 0.0001 respectively, but no signifcant difference was found between the mean difference of the two groups p = 0.95
5 Conclusions
A total of 257 samples during pre - hospital evacuation were collected for the study analysis
5.1 The analgesic effect of both ketamine and morphine were clear There was a statistically significant difference between VAS1 and VAS2 for the total samples as well
as the individual groups assigned to ketamine and morphine
The analgesic effect of ketamine was the same as the analgesic effect of morphine
No signifcant difference was found between the mean difference of the two groups
Trang 105.2 The analgesic effects of ketamine and morphine were clear by ISS, age and gender
5.3 The adverse effects of nausea and vomiting were much lower in the ketamine group than the morphine group (5% vs 30.77%) and (2.14% vs 27.25%), respectively
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