Comparison of the efficacy of lornoxicam and fentanyl in attenuating the hemodynamic response to laryngoscopy and intubation.

BACKGROUND AND OBJECTIVES: Laryngoscopy and intubation elicits huge spectrum of stress response which is hazardous in high-risk patients. Many drugs and techniques have been used to attenuate the stress response. Lornoxicam 16 mg is a potent nonsteroidal anti-inflammatory drug agent with analgesic potency equivalent to morphine 10 mg, fentanyl 100 μg and tramadol 100 mg. Lornoxicam has been found to attenuate stress response in some studies. We compared the lornoxicam with fentanyl in attenuating stress response.
MATERIALS AND METHODS: A double blind randomized controlled study was conducted on 60 adult patients of American Society of Anesthesiologist physical status 1 and 2. Group L (n = 30) receives injection lornoxicam 16 mg intravenous 30 min before induction, Group F (n = 30) receives injection fentanyl 2 μg/kg during induction. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) were recorded baseline (BL), before induction, every minute up to 5 min and at 10 min after intubation.
RESULTS: After intubation, there is a gradual decrease in SBP and DBP in both groups. The MAP was also comparable between the two groups except at 5 min and 10 min during which MAP recovered toward BL in Group L where as it remained low in Group F which was statistically significant (P < 0.05). Both the drugs have successfully attenuated the HR response.
CONCLUSION: Lornoxicam successfully attenuated the hemodynamic response to laryngoscopy and endotracheal intubation and is equally efficacious as fentanyl.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

The pressor response which is a part of huge spectrum of stress response during laryngoscopy and intubation following general anesthesia is due to sympathoadrenal activity as evidenced by increased heart rate (HR), blood pressure, and serum catecholamine concentrations, described in as early as 1940 by Reid and Brace.[1] These hemodynamic changes are usually transient, variable, and unpredictable. These changes may be of no consequence in healthy individuals, but either or both may be hazardous in patients with hypertension, myocardial ischemia, cerebrovascular diseases, and those with increased intraocular pressures.[2]

Various drugs and techniques have been used from time to time for attenuating the stress response including opioids[34] lidocaine[56] beta blockers[78] calcium channel blockers[9] vasodilators[10] α2 agonists[1112] However, no modality was devoid of drawbacks and limitations and the hunt for ideal drug continues.

Lornoxicam is a nonsteroidal anti-inflammatory drug (NSAID) with potent analgesic and anti-inflammatory activity that belong to oxicam group and acts by inhibiting cyclo-oxygenase 1 and 2 (COX-1 and COX-2).[13] Recently, many studies have proved its efficacy to attenuate the pressor response. We undertook this study to investigate the efficacy of lornoxicam in attenuating hemodynamic response to laryngoscopy and intubation.

MATERIALS AND METHODS

After obtaining Ethical Committee approval and patients informed consent, sixty patients aged 18–60 years of American Society of Anesthesiologist physical status 1 and 2 undergoing surgeries under general anesthesia and requiring orotracheal intubation were enrolled in this prospective, randomized double-blind study. Patients with body mass index >30, known allergy to NSAIDs, alcohol abuse, major systemic disease, coagulopathies, difficult airway, and those required two or more attempts at intubation were excluded from the study. Patients were randomly allocated to one of the two groups in a double-blind fashion to receive intravenous (i.v.) injection of either lornoxicam 16 mg diluted to 4 ml (Group L n = 30) 30 min before induction of anesthesia as the time taken by lornoxicam to reach peak plasma concentration is 30 min, 4 ml of saline at the time of induction and second group received 4 ml of saline 30 min before and injection fentanyl 2 µg/kg diluted to 4 ml at the time of induction.

Person administering the drugs was not involved in data collection to ensure double blindness of the study. As lornoxicam is yellow in color and fentanyl is a clear fluid, syringes containing both solutions were covered.

Patients were given the previous night with tab ranitidine 150 mg and tab diazepam 10 mg. No premedication was given in the morning of surgery to avoid hemodynamic changes caused by drugs other than study drugs.

In the preoperation room, i.v. infusion of lactated Ringer's solution 10 ml/kg was started. With noninvasive blood pressure (NIBP) monitor, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and HR were recorded before injection of a study drug as a baseline (BL) value. The study drug was administered as a bolus intravenously over 5 min and patient was monitored for any complications or side effects.

After 30 min the patients were wheeled into the operation theatre and were connected to a multipara monitor (BeneviewT8) having NIBP monitoring, electrocardiography and SpO2. Before induction of anesthesia SBP, DBP, MAP and HR were recorded as preinduction values. Patients were premedicated with injection glycopyrrolate 0.02 mg/kg, injection midazolam 0.05 mg/kg i.v. in both groups. Group L received 4 ml of normal saline and Group F received injection Fentanyl 2 µg/kg in 4 ml dilution before induction of anesthesia. After 3 min of preoxygenation, anesthesia was induced with injection propofol 2.5 mg/kg i.v. and injection vecuronium bromide 0.1 mg/kg i.v. to facilitate endotracheal intubation. All patients were mask ventilated for 4 min with 100% oxygen. A gentle laryngoscopy and orotracheal intubation was performed by an experienced anesthesiologist. All intubations were performed by a single anesthesiologist. Intubations requiring two or more attempts and those requiring more than 20 s were dropped from the study. Following intubation, the lungs were ventilated with 66% nitrous oxide in oxygen. SBP, DBP, MAP, and HR were recorded every minute up to 5 min and at 10 min after cuff inflation.

All measurements were completed before patient positioning, skin incision, administration of additional analgesic, urinary catheterization, and skin painting. After obtaining the data, patient group was revealed by person administering the drug. Patients in Group L received injection pentazocine 0.3 mg/kg i.v. before skin incision. At the end of surgery, muscle relaxation was reversed and patients were extubated. Patients were observed for 24 h postoperatively for NSAID related complications and shifted to ward.

Statistical analysis was performed using SPSS 21.0 version (IBM Corp. Released 2012. IBM SPSS Statistics for windows, version 21.0. Armonk, NY: IBM Corp). Numerical data are presented as mean ± standard deviation. Statistical comparisons among the groups were performed using unpaired t-test. The paired t-test was applied within the groups. The number of subjects enrolled was based on a power calculation of finding a 10% difference between two groups in MAP from BL values at alpha error of 0.05 and beta 0.1. The categorical data were expressed as numbers and percentages. The statistical significance was set at 5% level of significance (P < 0.05).

RESULTS

The two groups were comparable with respect to age, sex, and weight [Table 1]. The mean SBP and DBP were comparable in both the groups throughout the study period [Tables 2 and 3]. Both the drugs attenuated rise in SBP and DBP following intubation. The mean MAP was also comparable between the two groups except at 5 min and 10 min during which MAP recovered toward BL in Group L where as it remained low in Group F which was statistically significant (P < 0.05) [Table 4]. Both drugs have successfully attenuated the HR response to laryngoscopy and intubation [Table 5]. There was statistically significant fall in SBP, DBP, and MAP in both groups compared to their BL values [Figures 1–3]. In Group L, the mean HR has increased from BL at 1 min after intubation but it was not statistically significant (P > 0.05) thereafter HR has been successfully attenuated. In Group F, compared to preinduction values HR has increased at 1 min which is not statistically significant, thereafter HR has been successfully attenuated [Figure 4]. There were no side effects or complications from either drug during 24 h of observation period.

Table 1

Distribution of demographic characteristics in lornoxicam and fentanyl groups

Table 2

Changes in systolic blood pressure (mmHg)

Table 3

Changes in diastolic blood pressure (mmHg)

Table 4

Changes in mean arterial pressure (mmHg)

Table 5

Changes in heart rate (beats per minute)

Figure 1

Changes in systolic blood pressure

Figure 3

Changes in mean arterial blood pressure

Figure 4

Changes in heart rate

Changes in diastolic blood pressure

DISCUSSION

Laryngoscopy and intubation are considered most critical events during general anesthesia. It provokes transient but marked sympathetic and sympathoadrenal response. Since long it is known that opioids are an important part of balanced anesthesia to provide perioperative analgesia, but they cause dose dependent side effects such as nausea, vomiting, respiratory depression, bradycardia, and pruritus. Fentanyl has been used widely to attenuate stress response in different dosages and in various combinations with varying results depending on the dose and timing of administration. In a study by Chung et al.,[14] a comparison of fentanyl, esmolol and their combination for blunting the hemodynamic responses during rapid-sequence induction was done. They studied different dosages and combinations. They concluded that combination of a low dose fentanyl and esmolol provides an alternative to a higher dose of fentanyl. In a study by Ko et al.[15] the optimal time of injection of fentanyl was studied at 1 min, 3 min, 5 min, and at 10 min and they concluded that the most effective time to administer fentanyl to prevent circulatory responses to laryngoscopy and tracheal intubation was 5 min before tracheal intubation. In our study also injection fentanyl was administered 5 min before intubation.

NSAIDS are equally efficacious in providing perioperative analgesia but they produce side effects such as platelet dysfunction, gastric ulceration, hepatic, and renal dysfunction. NSAIDs are commonly administered as adjuvant during the preoperative period to improve the control of postoperative pain while reducing the need for opioid analgesics.[16]

Lornoxicam is a NSAID that belong to oxicam group; it acts by inhibiting COX-1 and COX-2. In addition, lornoxicam increases endogenous beta-endorphin and dynorphin levels producing central analgesic and anti-inflammatory effects. After intramuscular administration maximum plasma concentrations are achieved in 20–25 min. It is metabolized in liver by cytochrome P4502DC9 to inactive metabolites and has a shorter half-life of 3.5–4.5 h and hence has a better safety profile with regard to hepatic, renal, and gastrointestinal side effects.[17] Nørholt et al.[18] in his study compared the analgesic efficacy and tolerability of intramuscular injection of lornoxicam (4, 8 16 and 20 mg) with morphine (10 and 20 mg) in patients with moderate to severe pain following surgical removal of an impacted third molar. They concluded that analgesic efficacy of intramuscular lornoxicam at doses more than 4 mg was superior to placebo and at doses more than 8 mg was at least as effective as intramuscular morphine 20 mg. Ilias and Jansen[19] in his study, compared the i.v. injection of lornoxicam in dose of 4 mg and 8 mg and tramadol in dose of 50 mg in patients with moderate to intolerable postoperative pain following hysterectomy. They concluded that i.v. lornoxicam at a dose of 8 mg was superior to placebo and at least as effective as i.v. tramadol 50 mg in relieving the pain. Rosenow et al.[20] in his study compared i.v. lornoxicam 4 or 8 mg, pethidine 50 mg or isotonic distilled water in patients with moderate to severe pain after laminectomy. They concluded that lornoxicam 8 mg intravenously was as effective as pethidine 50 mg intravenously in relieving pain. Lornoxicam has been studied extensively in control of chronic pain[21] and acute postoperative pain[2223] In a study by Daabiss et al.[24] lornoxicam 8 mg, 16 mg and fentanyl 100 μg were compared for perioperative analgesic effect in day-care ear, nose, throat surgeries and they found that lornoxicam 16 mg was comparable to fentanyl as intraoperative analgesic and more effective than fentanyl in preventing early postoperative pain and the incidence of postoperative nausea and vomiting (PONV) was also less. There are only few studies on effect of lornoxicam on intubation response. In a study by Riad and Moussa[25] lornoxicam 8 mg when added to fentanyl in elderly patients attenuated the stress response to laryngoscopy and intubation.

Hence, we studied the efficacy of lornoxicam 16 mg in preventing stress response to laryngoscopy and intubation compared to fentanyl. We found that in both the groups there was no statistically significant increase in SBP, DBP, and MAP after laryngoscopy and intubation, however the HR increased at 1 min compared to BL in both groups which was not statistically significant, thereafter the HR progressively decreased to reach their BL values. In a study by Daabiss et al.,[26] lornoxicam was compared with placebo to attenuate the stress response. In agreement with our study they found that lornoxicam successfully attenuated the stress response to laryngoscopy and intubation and they also found that the HR increased at 1 min after intubation which was not statistically significant, later the HR decreased gradually toward BL. In our study, the mean MAP was also comparable between the two groups except at 5 min and 10 min during which MAP recovered toward BL in Group L where as it remained low in Group F which was statistically significant (P < 0.05). This may be due to the vasodilatory and myocardial depressant effect of injection propofol and fentanyl. The propofol used to induce anesthesia causes hypotension this will ameliorate the stress response. We could not study the serum catecholamine levels as the facilities were not available in our institution. This could be considered as a limitation of the present study. As the sample size we studied is less, it requires further metaanalysis. As we studied lornoxicam 16 mg to attenuate the stress response there is a further scope to study the different dosages of lornoxicam and to study the effects of the drug in reducing PONV and postoperative pain.

CONCLUSION

Lornoxicam successfully attenuated the hemodynamic response to laryngoscopy and endotracheal intubation and is equally efficacious as fentanyl.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.