Báo cáo nghiên cứu khoa học: "Đánh giá ảnh hưởng của ketamine (thuốc giảm đau) trong chăm sóc chấn thương prehospital. Một thử nghiệm lâm sàng ở Quảng Trị, Việt Nam" potx

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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 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


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care 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
measures (airway cut-down, chest tube placement etc.).


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Patients 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:


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One intramuscular dose of morphine 10 mg (adults).
Sample size
n =

2
2
2/2/1
)).(1(.
d
ZZppZ




p
1
= 0.20: nausea/vomit rate by morphine
p
2
=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
VAS1 7.07 7.26 6.84
VAS2 3.78 3.82 3.72
Mean Difference 3.29 3.44 3.11
Std Error 0.12 0.16 0.18
95% CI 3.06 - 3.53 3.14 - 3.75 2.75 - 3.48
N 257 140 116
Correlation 0.033 0.106 -0.06
t-Ratio 27.49 22.09 16.82
DF 256 139 116


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Total n = 257 Ketamine n=140 Morphine n=117
Prob > |t| <.0001 <.0001 <.0001
Test across group P= 0.1679
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

Moderate Major Severe
Ketamine

Morphine

Ketamine Morphine

Ketamine

Morphine

VAS1 7.05 6.80 7.35 6.73 7.55 6.92
VAS2 3.70 3.69 4.22 4.09 3.89 3.65
Mean
Difference
3.35 3.11 3.12 2.65 3.66 3.27
Std Error 0.21 0.26 0.41 0.59 0.27 0.30
Upper95% 3.76 3.62 4.03 3.90 4.21 3.87
Lower95% 2.93 2.59 2.22 1.39 3.11 2.67
N 76 55 12 15 52 47
Correlation 0.08 -0.14 0.28 -0.16 0.11 0.05
t-Ratio 16.04 12.06 7.58 4.52 13.39 11.00
DF 75 54 11 14 51 46
Prob > |t| <.0001 <.0001 <0.0001 <0.0005 <.0001 <.0001
Test Across
Groups
Prob>F Prob>F Prob>F
Mean
Difference
0.47 0.53 0.33
3.3. Matched pairs analysis by Gender
Table 3.3. Matched pairs analysis by Gender
GENDER MALE FEMALE
VAS1 7.07 7.15 6.85
VAS2 3.78 3.81 3.70
Mean Difference 3.29 3.34 3.15


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GENDER MALE FEMALE
Std Error 0.12 0.13 0.26

Upper95% 3.53 3.61 3.67
Lower95% 3.06 3.08 2.62
N 257 191 66
Correlation 0.03 0.06 -0.0271
t-Ratio 27.49 25.00 12.04
DF 256 190 65
Prob > |t| <.0001 <.0001 <.0001
Test Across Groups Prob>F
Mean Difference 0.16
3.4. Nausea/vomitting
Table 3.4. Nausea/vomitting frequency of Ketamine and Morphine
Nausea Frequence Vomit Frequence
KETAMINE n=140 7 5.00 3 2.14 P<0.005
MORPHINE n=117 36 30.77 32 27.35
3.5. Matched pairs analysis by age (<15)
Table 3.5. Matched pairs analysis by age (<15)
AGE <15 Ketamine Morphine Male Female
VAS1 7.19 7.31 6.94 7.07 7.47
VAS2 4.15 4.02 4.4 4.28 3.82
Mean
Difference
3.04 3.29 2.54 2.79 3.65
Std Error 0.45 0.61 0.58 0.53 0.82
Upper95% 3.97 4.60 3.95 3.94 5.77
Lower95% 2.11 1.98 1.13 1.65 1.54
N 21 14 7 15 6
Correlation 0.02 0.04 0.11 0.11 -0.146
t-Ratio 6.82 5.42 4.42 5.23 4.44

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AGE <15 Ketamine Morphine Male Female
DF 20 13 6 14 5
Prob > |t| <.0001 0.0001 0.0045 0.0001 0.0068
Test Across
Groups
Prob>F F Ratio Prob>F
Mean
Difference
0.45 0.75 0.40
3.6. Matched pairs analysis by age (15-54)
Table 3.6. Matched pairs analysis by age (15-54)
Age (15-54) KETAMIN MORPHIN MALE FEMALE

VAS1 7.08 7.25 6.87 7.17 6.70
VAS2 3.81 3.80 3.82 3.83 3.73
Average
difference
3.27 3.45 3.05 3.34 2.97
Standard error

0.14 0.18 0.23 0.15 0.38
95% CI 2.99 - 3.55 3.09 - 3.82 2.60 - 3.49 3.04 -3.65

2.20 -3.74

Sample size 187 102 85 152 35
Correlation 0.018 0.13 -0.113 0.05 -0.1069
t-test 22.70 18.73 13.50 21.63 7.836
Degrees of

Freedom (df)
186 101 84 151 34
P
value
<.0001 <.0001 <.0001 <.0001 <.0001
Test among
groups
0.173 1.021
3.7. Matched pairs analysis by age (>=55)
Table 3.7. Matched pairs analysis by age (>=55)
AGE>=55 KETAMIN

MORPHIN MALE FEMALE
VAS1 6.98 7.25 6.71 7.04 6.91
VAS2 3.49 3.78 3.21 3.35 3.63
Average difference

3.48 3.47 3.5 3.69 3.29


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AGE>=55 KETAMIN

MORPHIN MALE FEMALE
Standard error 0.24 0.32 0.37 0.25 0.41
95% CI 3.00 - 3.97

2.82 - 4.12

2.74 - 4.26 3.18 - 4.20 2.45 - 4.13

Sample size 49 24 25 24 25
Correlation 0.089 0.009 0.06 0.09 0.098
t-test 14.55 11.10 9.54 14.93 8.08
Degrees of
Freedom (df)
48 23 24 23 24
P
value
<.0001 <.0001 <.0001 <.0001 <.0001
Test among groups

0.95 0.41
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 VAS
1
and VAS
2
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
cases of vomitng, a rate of 2,14%. In the morphine group (n= 177) there were 36 cases


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of 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.


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5.2. 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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