Gabapentin attenuates the pressor response to direct laryngoscopy and tracheal intubation
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British Journal of Anaesthesia 96 (6): 769–73 (2006)
doi:10.1093/bja/ael076 Advance Access publication April 4, 2006
Gabapentin attenuates the pressor response to direct
laryngoscopy and tracheal intubation
A. Fassoulaki*, A. Melemeni, A. Paraskeva and G. Petropoulos
Department of Anaesthesiology, Aretaieio Hospital, Medical School, University of Athens,
76 Vassilissis Avenue, 11528 Athens, Greece
*Corresponding author. E-mail: fassoula@aretaieio.uoa.gr
Background. Laryngoscopy and tracheal intubation increase blood pressure and heart rate
(HR). The aim of the present study was to investigate the effect of gabapentin when given before
operation on the haemodynamic responses to laryngoscopy and intubation.
Methods. Forty-six patients undergoing abdominal hysterectomy for benign disease were
randomly allocated to receive gabapentin 1600 mg or placebo capsules at 6 hourly intervals
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starting the day (noon) before surgery. Anaesthesia was induced with propofol and cis-
atracurium. Systolic, diastolic arterial blood pressures (SAP, DAP) and heart rate (HR) were
recorded before and after the anaesthetic and 0, 1, 3, 5 and 10 min after tracheal intubation.
Results. SAP was significantly lower in the gabapentin vs the control group 0, 1, 3, 5 and 10 min
after intubation [128 (27) vs 165 (41), P=0.001, 121 (14) vs 148 (29), P=0.0001, 115 (13) vs 134 (24),
P=0.002, 111 (12) vs 126 (19), P=0.004 and 108 (12) vs 124 (17), P=0.001 respectively]. DAP also
was lower in the gabapentin group 0, 1, 3, and 10 min after intubation [81 (18) vs 104 (19),
P=0.0001, 77 (9) vs 91 (16), P=0.001, 71 (10) vs 84 (13), P=0.001 and 67 (10) vs 79 (12), P=0.004].
HR did not differ between the two groups at any time [82 (11) vs 83 (15), 79 (10) vs 80 (12), 86 (17)
vs 92 (10), 82 (11) vs 88 (10), 81 (12) vs 81 (11), 77 (13) vs 79 (13), and 75 (15) vs 78 (12)].
Conclusion. Gabapentin, under the present study design attenuates the pressor response but
not the tachycardia associated with laryngoscopy and tracheal intubation.
Br J Anaesth 2006; 96: 769–73
Keywords: drugs, gabapentin; heart, dysrhythmia, tachycardia; larynx, laryngoscopy, intubation;
pressor response
Accepted for publication: February 16, 2006
Laryngoscopy and intubation are associated with cardio- randomized controlled trials to treat acute postoperative pain
vascular changes such as hypertension, tachycardia, dys- and to reduce the postoperative opioid requirements.13–17
rhythmias and even, myocardial ischaemia1 and increased While performing these studies with gabapentin, we noticed
circulating catecholamines.2 that some patients were haemodynamically stable.
Several techniques have been proposed to prevent or The present study was designed as double-blind random-
attenuate the haemodynamic responses following laryngo- ized controlled trial to investigate the effect of gabapentin
scopy and intubation, such as deepening of anaesthesia,1 on the changes in blood pressure and heart rate (HR)
omitting cholinergic premedication,3 pretreatment with observed during laryngoscopy and tracheal intubation.
vasodilators such as nitroglycerin,4 beta-blockers,5 calcium
channel blockers6 and opioids.7–9 The most recent studies
aiming at controlling or attenuating the haemodynamic Methods
response to intubation and laryngoscopy focused on the
effect of remifentanil at different dosing regimens.10–12 Subjects
Gabapentin is a relatively new drug, which was intro- After obtaining approval from the Hospital Ethics Com-
duced as antiepileptic but proved to be effective in control- mittee and patients’ informed consent, 46 patients under-
ling neuropathic pain. The drug is well tolerated with limited going abdominal hysterectomy for benign disease were
side-effects, as compared with older antiepileptics such as allocated randomly to the gabapentin or the control
carbamazepine. More recently gabapentin has been used in group. Exclusion criteria included anticipated difficult
The Board of Management and Trustees of the British Journal of Anaesthesia 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.orgFassoulaki et al.
intubation, ASA physical status III or greater, hiatus hernia Study population size
and gastro-oesophageal reflux, patients with body weight Preliminary sample size estimation based on initial pilot
more than 20% of the ideal body weight, age more than observations indicated that approximately 20–23 patients
59 yr, and consumption of antihypertensive drugs, sedatives, should be included in each group, in order to ensure
hypnotics, antidepressants, drugs with effect on the nervous power 0.80 for detecting clinically meaningful reductions
system, except those determined by the study protocol. in HR and SAP by 10–20%. Alpha error was assumed to be
0.05. Estimated standard deviations were approximately
11 and 20 for HR and SAP, respectively. Sample size
Randomization and treatment estimation was performed using the following software
Sixty opaque envelopes containing the code odds or even available on-line: (i) Power Calculator (UCLA Department
numbers for the Athina or Foivos groups, respectively, were of Statistics, calculators.stat.ucla.edu/powercalc/) and
prepared and sealed. Gabapentin 400 mg or placebo cap- (ii) Java applets for power and sample size (provided
sules were kept in vases labelled as Athina and Foivos (the by Professor R.V. Lenth, Department of Statistics and
mascots of the Olympic Games, Athens 2004), respectively. Actuarial Science, University of Iowa, www.stat.uiowa.
After opening an envelope the day before surgery patients edu/-rlenth/power).
were randomized to the Athina or to the Foivos group
accordingly and treated with the capsules from the vase Statistics
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labelled as Athina or Foivos, respectively. Gabapentin
400 mg or placebo capsules were administered at noon, Patients’ characteristics between the two groups were
18 h, and 24 h the day before surgery and at 6 AM, the compared with Student’s t-test for unpaired observations.
ANOVA with repeated measures was used to compare the
morning of surgery. Envelope labelling, placebo capsules,
vase filling and group allocation were done by an anaes- changes in SAP, the DAP and HR values. Individual inter-
thetist who was not aware of the study protocol and did not group comparisons, where appropriate, were done using
participate in the study. The same anaesthetist distributed Scheffe’s test.
the capsules to the patients according to the group allocation PTracheal intubation and gabapentin Table 2 SAP before and after i.v. anaesthetics, and immediately (0 min), 1, 3, 5 and 10 min after tracheal intubation and cuff inflation in the gabapentin and the control group. Values are mean (SD) and 95% CI. ANOVA with regard to group: F=10.018, df=1, P=0.003. ANOVA with regard to time: F=22.470, df=3.374 P=0.0001. *P
Fassoulaki et al.
hypertension and tachycardia during rapid sequence our patients needed active treatment for hypotension during
induction. However, remifentanil 1 mg kg 1 was effective the study period.
while 1.25 mg kg 1 in some patients caused hypotension.11 We studied patients up to 59 yr as elderly patients take
Finally, Hall and colleagues12 reported that 0.5 mg kg 1 more often drugs such as antidepressants, hypnotics and
over 30 s followed by infusion of 0.25 mg kg 1 min 1 was antihypertensives. Older patients also exhibit increased
associated with slight changes in haemodynamic responses sensitivity to drugs9 and the cardiovascular effects of gaba-
after laryngoscopy and orotracheal intubation. pentin are not studied extensively. Aged patients should
When assessing techniques to ameliorate the cardio- comprise a different group with doses of gabapentin
vascular responses to intubation the drugs used to induce probably adjusted to age.
anaesthesia may influence the results. We induced anaes- The mechanism by which gabapentin attenuates the
thesia with propofol, which produces bradycardia. Thus pressor response to laryngoscopy and intubation is unknown.
tachycardia resulting from intubation may have been attenu- The drug inhibits membrane voltage-gated calcium chan-
ated by propofol in both groups covering such a possible nels, thus acting in a manner similar to calcium channel
effect of gabapentin on the HR. Omission of opioids during blockers.22 To our knowledge no randomized controlled
induction of anaesthesia in patients ASA I and II should trial has as primary aim the cardiovascular effects of gaba-
not be a concern. Besides, propofol produces hypotension pentin. As gabapentin is recently used as adjuvant for acute
more than thiopental and bradycardia, which may com- postoperative pain studies on its haemodynamic effects will
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pensate in part the cardiovascular changes attributable to be more than welcome. Also, patients who are treated with
laryngoscopy and tracheal intubation. the drug before operation will benefit from its effect on the
We did not measure stress mediators such as endogenous pressor response to laryngoscopy and tracheal intubation.
plasma catecholamines or cortisone, and we did not score In conclusion, pretreatment with gabapentin under the
sedation. These can be considered as limitations of the dose given and the present study design attenuates the
study. Though measurements of endogenous catecholam- pressor response to laryngoscopy and intubation of the tra-
ines would give useful information, scoring sedation before chea. It has no effect on the changes in HR. As the use of
induction of anaesthesia would interfere with the double- gabapentin in the peri-operative setting is becoming more
blinding of the study. frequent more studies focusing on its cardiovascular effects
As we pretreat our patients with four doses of gabapentin and its effect on stress mediators are needed.
as adjuvant to prevent acute and chronic postoperative
pain14 15 we investigated whether the same pretreatment
regime may attenuate the cardiovascular response to intuba- Acknowledgement
tion and laryngoscopy. Gabapentin originally introduced as The present study was supported from Departmental sources.
antiepileptic, is effective in neuropathic pain and most
recently has been evaluated as analgesic, anti-hyperalgesic,
or both, perioperatively.13–17 However, only few data in the
literature are available regarding the effect of gabapentin on References
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