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Original Article

Lornoxicam attenuates the haemodynamic responses to laryngoscopy and tracheal intubation in the elderly*

Riad, W.*; Moussa, A.

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European Journal of Anaesthesiology: September 2008 - Volume 25 - Issue 9 - p 732-736
doi: 10.1017/S0265021508004286
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Abstract

Introduction

Lornoxicam (rINN, 6-chloro-4-hydroxy-2-methyl-N-2-pyridyl-2H-thieno {2, 3-e}-1, 2-thiazine-3-carboxy-amide-1, 1-dioxide) is a novel non-steroidal anti-inflammatory drug (NSAID) with a marked analgesic property [1]. Lornoxicam (Xefo®; Nycomed Pharma AS, Roskilde, Denmark) is a yellow crystalline substance with a dissociation constant (pKa) of 4.7 and a partition coefficient of 1.8 with a neutral pH (7.4) [2]. It belongs to the chemical class of the oxicams, like piroxicam and tenoxicam, but with more potent clinical properties [3]. Lornoxicam is rapidly eliminated, having a short plasma elimination half-life of 3-5 h [4]. Clinically, a single dose of 4 or 8 mg is used. It has been shown to be as effective as 10 mg morphine when used at a dose of ≥8 mg [5]. In the treatment of postoperative pain, Lornoxicam has been shown to be as effective as meperidine [4].

Laryngoscopy and subsequent tracheal intubation result in the activation of the sympathetic nervous system due to stimulation of somatic and visceral nociceptive afferents of the epiglottis, hypopharynx, peritracheal area and vocal cords. The ultimate effect of such nociceptive input is that of cardiovascular stimulation, which results in an increase in blood pressure (BP) and heart rate (HR) [6]. Several techniques have been proposed to prevent or attenuate the haemodynamic responses following laryngoscopy and tracheal intubation such as deepening of anaesthesia [7], omitting cholinergic premedication [8], pretreatment with vasodilators such as nitroglycerine [9], β-blockers [10], α2 agonists such as clonidine [11] and opioids [12]. Opioids have been shown to be effective agents in blunting these stimulatory effects on the cardiovascular system. Unfortunately, opioids have well-known side-effects such as hypotension, bradycardia and postoperative nausea and vomiting, respiratory depression and muscle rigidity [13]. Elderly patients are more sensitive to the cardiodepressant action of anaesthetic agents than young patients; hence, minimizing the perioperative adverse events is of utmost importance [14]. Therefore, other agents have been tried to replace or to reduce the opioid dose in blunting the stress response to laryngoscopy and tracheal intubation. The aim of this study was to demonstrate the effect of preoperative administration of Lornoxicam on haemodynamic changes during laryngoscopy and tracheal intubation in the elderly.

Methods

After obtaining the approval of the Hospital Research and Human Ethics Committees and patient's informed consent, 50 elderly patients, aged between 65 and 75 yr, ASA class I and II undergoing general anaesthesia requiring tracheal intubation for elective surgical procedures were enrolled in this randomized, double-blind, placebo-controlled study. Exclusion criteria included anticipated difficult tracheal intubation, patients at risk of regurgitation or pulmonary aspiration, e.g. hiatus hernia, patients with body mass index more than 30 kg m−2, intake of analgesics less than 24 h before operation, patients with renal and hepatic impairment, receiving medications known to affect BP and HR, e.g. β-blockers and allergy to NSAIDs.

All patients fasted overnight but were allowed oral intake of clear fluids up to 3 h before surgery. All patients received no premedication. Patients were maintained normothermic during the perioperative period. In the holding area, an intravenous (i.v.) cannula was inserted and an i.v. infusion of Lactated Ringer's and 5% Dextrose (D5LR) (Baxter Healthcare Corporation, Deerfield, IL, USA) was started. The standard monitoring with continuous electrocardiography, non-invasive arterial BP monitoring, and pulse oximetry were used for both groups. Patients were allocated randomly according to a computer-generated randomization and sealed envelope technique into two groups to receive either Lornoxicam 8 mg or placebo half an hour before surgery. The injections are different in appearance (placebo is clear while Lornoxicam is yellow), so to maintain observer blindness, the syringes were covered and the medications were administered by a different anaesthetist who was not involved in the study. Because the depth of anaesthesia at the time of tracheal intubation may influence the cardiovascular response [7], the induction technique was standardized. On arrival in the operating theatre and after preoxygenation, anaesthesia was induced with fentanyl 1 μg kg−1 and propofol 1.5-1.75 mg kg−1. Atracurium 0.5 mg kg−1 was given to facilitate tracheal intubation and intubation performed when the train-of-four (TOF) count was zero using quantitative neuromuscular transmission (Datex-Ohmeda NMT module, Stirling, UK). Systolic and diastolic blood pressure, mean arterial pressure (MAP), and HR were recorded before and after administration of the i.v. anaesthetic, immediately after tracheal intubation and cuff inflation and 1, 3, 5 and 10 min later. During the observation period, a fresh gas flow of 1.5 L min−1 was used and the end-tidal carbon dioxide was maintained at 35-40 mmHg. To minimize bias, all tracheal intubations were performed by a single anaesthetist (AM), the duration of laryngoscopy and tracheal intubation limited to the minimum possible time and were recorded. For the purpose of the study, intubation time was defined as the period from termination of manual ventilation using a facemask to restarting of ventilation through the endotracheal tube. This was recorded by a research nurse using a stopwatch. Patients requiring more than 120 s to achieve successful tracheal intubation were excluded from the study. Anaesthesia was maintained using sevoflurane and oxygen : air mixture. At the completion of the surgical procedure, residual neuromuscular block was reversed with 0.05 mg kg−1 neostigmine and 5 μg kg−1 glycopyrrolate and the patient transferred to the recovery room.

Statistical analysis

The results were analysed using the Statistical Package for Social Science for Windows version 12 (SPSS Inc., Chicago, IL, USA). Sample size calculation showed that 25 patients should be included in each group, in order to have a 20% change in HR and BP. The α error was assumed to be 0.05 and type II error was set at 0.20. Sample size estimation was performed using Power Calculator (UCLA Department of Statistics, http://www.stat.ubc.ca/˜rollin/stats/ssize). Numerical data were expressed as mean ± SD and were analysed using the unpaired, two-tailed t-test. Categorical data were expressed as numbers and compared using the χ2-test. P value of 0.05 was used as the level of significance.

Results

A total of 50 patients were enrolled in this study. Patient characteristics are shown in Table 1. The groups were similar with respect to age, height, weight, gender and ASA classification. All tracheal intubations were successful at the first attempt with mean duration of intubation 50.8 and 52.8 s (range 35-67 s) in Lornoxicam and control groups, respectively.

Table 1
Table 1:
Patient characteristics.

After anaesthesia induction and during the entire observation period HR was significantly greater in the control group compared with the Lornoxicam group (Fig. 1) (P < 0.05). On the other hand, systolic and diastolic blood pressure and MAP showed insignificant drop after induction of anaesthesia and before tracheal intubation. Inter-group comparisons showed a significantly higher systolic BP at 3, 5 and 10 min after tracheal intubation in the control group (P value < 0.05). Diastolic BP and MAP were significantly lower in the Lornoxicam group at 1 and 5 min after laryngoscopy and tracheal intubation (Fig. 1) (P value < 0.05).

Figure 1
Figure 1:
Heart rate (HR) and blood pressure (BP) changes. SBP: systolic BP; DBP: diastolic BP; MAP: mean arterial pressure. Points represent mean ± SD, *P value < 0.05.

Discussion

These results suggest that preoperative administration of Lornoxicam half an hour before surgery significantly decreased the HR and BP response to laryngoscopy and tracheal intubation in the elderly.

Laryngoscopy and tracheal intubation are the gold standard during the induction of general anaesthesia. However, securing the patient's airway is associated with haemodynamic changes. We strive to make anaesthetic induction as smooth as possible in order to avoid this hazardous effect. Elderly patients, being more atherosclerotic with more vulnerable baroreceptors, are more prone to experience substantial haemodynamic changes during laryngoscopy and tracheal intubation [14]. The cardiovascular responses to laryngoscopy and tracheal intubation are well established in the literatures [15]. In agreement with our results, Tsubaki and colleagues reported a marked increase of circulatory and catecholamine responses with direct laryngoscopy [16]. In a study by Kihara and colleagues, the haemodynamic response to direct laryngoscopy was compared with that with the intubating laryngeal mask and the Trachlight device (Laerdal Medical Corporation, Wappingers Falls, NY, USA). Their results showed that HR increased compared with preoperative baseline values in all groups. However, both systolic and diastolic pressure increased after tracheal intubation for 2 min with highest values in the hypertensive group receiving direct laryngoscopy [17]. Shribman and colleagues reported that laryngoscopy alone or associated with tracheal intubation produces an increase in arterial pressure and catecholamine levels while tracheal intubation significantly increases HR [18]. Kahl and colleagues reported that direct laryngoscopy produces a marked stress response secondary to major distention of supraglottic tissues [19].

Lornoxicam has demonstrated clinical efficacy in relieving chronic pain associated with osteoarthritis [20], rheumatoid arthritis and ankylosing spondylitis [21]. In the treatment of postoperative pain, Lornoxicam has been shown to be as effective as morphine [5], tramadol [22] and meperidine [4]. In the postoperative setting, Lornoxicam has been well tolerated with a tolerability profile similar to diclofenac [20], but superior to that of indomethacin [21]. We gave Lornoxicam half an hour before induction of anaesthesia as the time taken to reach peak plasma concentration (Tmax) was determined to be 0.5 h [23].

The mechanism by which Lornoxicam attenuates the pressor response to laryngoscopy and tracheal intubation is unknown. It might be attributable to its analgesic action mediated through the antiprostaglandin effect of COX inhibition. To the best of our knowledge, this is the first controlled study to report the effect of Lornoxicam on the pressor response in the elderly. Ankier and colleagues performed a pharmacokinetic study in elderly volunteers aged between 66 and 79 yr. They administered 4 mg Lornoxicam once daily for 9 days and reported a shorter elimination half-life of 2.5 h compared to young subjects and no accumulation after multiple doses [23]. Because of a lack of previous literature on the effect of Lornoxicam during induction of anesthesia in the elderly, fentanyl was given in a dose of 1 μg kg−1 although it would have been more informative if narcotics had been omitted completely. Also measurement of serum catecholamine would have been useful. These could be considered as a limitation for the present work. In conclusion, we found that pretreatment with Lornoxicam in the dose given and with the present study design attenuates the pressor response to laryngoscopy and tracheal intubation of the trachea in elderly patients.

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Keywords:

ELDERLY; ANAESTHESIA, stress response; INTUBATION INTRATRACHEAL; LORNOXICAM

© 2008 European Society of Anaesthesiology