Secondary Logo

Journal Logo

Original Paper

Attenuation of the haemodynamic responses to noxious stimuli in patients undergoing cataract surgery. A comparison of magnesium sulphate, esmolol, lignocaine, nitroglycerine and placebo given i.v. with induction of anaesthesia

van den Berg, A. A.; Savva, D.*; Honjol, N. M.

Author Information
European Journal of Anaesthesiology: March 1997 - Volume 14 - Issue 2 - p 134-147

Abstract

Introduction

Patients undergoing cataract extraction under general anaesthesia are usually middle aged or elderly, are often receiving treatment for diabetes, hypertension, ischaemic heart disease or a combination of these diseases, and may be subjected to tracheal intubation as part of their anaesthetic technique. Both tracheal intubation following induction of anaesthesia and tracheal extubation at the end of anaesthesia cause increases in heart rate (HR) and blood pressure (BP) [1,2], which may be particularly undesirable in this group of patients. A rise in HR may reduce coronary artery perfusion [3] and predispose to myocardial ischaemia [4]; a large increase or decrease in the systolic arterial pressure may result in cerebral infarction or thrombosis, or in acute left ventricular failure [5]; a decrease in the diastolic arterial pressure may reduce coronary perfusion and predispose to myocardial ischaemia [3]. The rate-pressure product (RPP=systolic blood pressure × heart rate) and the pressure-rate quotient (PRQ=mean blood pressure ÷ heart rate) are derived parameters which may be associated with ischaemic electrocardiographic changes when the RPP exceeds 12 000 [6,7] and when the PRQ is less than one [8].

Elderly patients (especially those suffering from diabetes, hypertension or ischaemic heart disease) may be especially prone to large changes in HR and BP during induction of anaesthesia. A variety of medications have been used to attenuate the stress responses caused by laryngoscopy and intubation. Beta adrenoreceptor antagonists given i.v. [1,9], lignocaine applied topically [10] or given i.v. [11], short acting analgesics given i.v. [12,13], direct acting vasodilators given i.v. [14] or applied transcutaneously [15], calcium antagonists given orally [16] or sublingually [17], alpha-2 adrenoreceptor agonists given orally [18], inhibitors of catecholamine release given i.v. [19] and angiotensin converting-enzyme inhibitors given sublingually [20] prior to laryngoscopy and intubation all reduce these responses. However, all of these drugs have different durations of action which may influence cardiovascular stability during surgery following the induction of anaesthesia. The longer acting drugs may also have a residual effect at the end of surgery, which may influence the haemodynamic responses to extubation.

This article reports a placebo controlled, randomized, double-blind study which was undertaken to compare the effects on HR, BP, RPP, and PRQ of a single i.v. bolus injection of magnesium sulphate (unknown half-life, duration of action about 30 min), esmolol (distribution and elimination half-lives of 2 and 9 min respectively, unpublished duration of action), lignocaine (distribution and elimination half-lives of 30 min and 60–120 min respectively, unpublished duration of action) and glyceryl trinitrate (GTN, distribution half-life 4 min, unpublished elimination half-life or duration of action) [21,22] given with induction of anaesthesia for cataract surgery. The study aimed to compare the haemodynamic responses of healthy and diseased patients to the effects of the test drugs, to assess the comparative effects of the drugs on the stimuli inflicted during laryngoscopy, tracheal intubation, subsequent anaesthesia and surgery, and ultimately, bandaging of the eye and tracheal extubation at the end of surgery.

Lignocaine and magnesium sulphate were tested in doses (1.5 mg kg−1 and 40 mg kg−1 respectively) which have been shown to attenuate the cardiovascular responses to tracheal intubation [23,24]. Esmolol was used in a dose (4 mg kg−1) which compares with that shown to be efficacious [25] and, in the absence of guidelines from previous studies, GTN was used in a dose (7.5 μg kg−1) recommended by our cardiac anaesthetic colleagues.

Method

The study was approved by the Research and Ethical Committee of the Riyadh Al Kharj Hospital Programme, and all patients, or their guardians, gave informed consent. Those studied were ASA grade I-III middle-aged to elderly healthy patients, as well as those receiving treatment for diabetes, hypertension, ischaemic heart disease or a combination of these diseases. All patients were scheduled to undergo cataract extraction under general anaesthesia, and were considered to be unsuitable for local (peribulbar) analgesia because of senility, language barrier, chronic cough, renal failure, or an estimated inability to remain immobile in the supine position for 90 min. Patients were considered to have ischaemic heart disease if they had a history of myocardial infarction, angina or electrocardiographic changes suggestive of ischaemic heart disease. Patients with diabetes were considered fit for surgery if fasting blood sugars were 3–8 mmol L−1, and those with hypertension were deemed adequately controlled if blood pressure on the day prior to surgery was less than 140/90.

On arrival in the operating theatre each patient was randomly allocated with respect to sex, type of disease (diabetes, hypertension, ischaemic heart disease or any combination of these diseases) and nature of treatment (insulin or oral antidiabetic drugs, beta adrenoreceptor antagonists or other antihypertensive drugs, or any cardioactive drug) to receive one of the five test drugs. The drugs were prepared by an assisting anaesthetist in coded 10 mL syringes and administered by a second anaesthetist who was blind to the nature of the test drug. Each 10 mL syringe contained either (1) 10 mL isotonic saline, (2) 8 mL magnesium sulphate (500 mg mL−1) plus 2 mL isotonic saline, (3) 1.6 mL esmolol (250 mg mL−1) plus 8.4 mL isotonic saline, (4) 10 mL 1.5% lignocaine (15 mg mL−1) or (5) 1.5 mL glyceryl trinitrate (0.5 mg mL−1) plus 8.5 mL isotonic saline.

All patients were premedicated with temazepam (10 mg) orally and a eutectic mixture of local anaesthetic (EMLA) was applied topically to the dorsum of the left hand 1 h pre-operatively. In the operating theatre ECG monitoring, pulse oximetry and non-invasive blood pressure monitoring (Critikon Dinamap 1846 SX, Tampa, FL, USA) were commenced. An i.v. cannula was inserted into a vein on the dorsum of the left hand, and Ringer lactate or isotonic saline infused to non-diabetics and diabetics, respectively, at a rate of 8 mL kg−1 h−1. After preoxygenation for 2 min, anaesthesia was induced with thiopentone (4.0 mg kg−1), atracurium (0.6 mg kg−1), diluted prochlorperazine 1 mg mL−1 (0.1 mg kg−1) [26] and diluted nalbuphine 2 mg mL−1 (0.2 mg kg−1), all injected i.v. at a rate of 1 mL sec−1. Immediately thereafter, the test drug was injected at the same rate. Each patient received either isotonic saline (0.1 mL kg−1), magnesium sulphate (40 mg kg−1), esmolol (4.0 mg kg−1), lignocaine (1.5 mg kg−1) or glyceryl trinitrate (7.5 μg kg−1).

The patient's lungs were then manually ventilated with nitrous oxide (66%) in oxygen and isoflurane (0.6%) for 60 s, after which laryngoscopy was performed, and the patient's larynx and upper trachea sprayed with lignocaine 10% (1 puff per 10 kg−1). Manual ventilation was continued for a further 60 s [27], following which laryngoscopy and tracheal intubation were performed by the anaesthetist who had administered the anaesthetic and test drugs.

Anaesthesia was maintained with nitrous oxide 66% and isoflurane 0.6% in oxygen. Ventilation was controlled using an Ohmeda AV7700 ventilator (Steeton, England) with a respiratory rate of 8 to 12 breaths min−1, and I:E rate of 1:3, a tidal volume of 10 mL kg−1, and a fresh gas flow of 100 mL kg−1 min−1 delivered via a Bain system to maintain an end-tidal carbon dioxide tension of 4.0 to 5.0 kPa. A heart rate of <50 beats min−1 was treated with atropine (0.003 mg kg−1), a rise in systolic blood pressure of >20% above the preinduction base-line level was treated with labetalol (0.1 mg kg−1) and a fall in the systolic blood pressure of >30% below the base-line level was treated with ephedrine (0.1 mg kg−1).

On completion of eye bandaging at the end of surgery, residual neuromuscular blockade was reversed with neostigmine (0.04 mg kg−1) and atropine (0.02 mg kg−1). The patient's lungs were then ventilated with 100% oxygen at a rate of 3 breaths min−1 until the onset of spontaneous breathing, whereupon the pharynx was suctioned using a Yankeur sucker, the endotracheal tube removed, and the patient given 100% oxygen to breathe via a facemask.

Records were made, prior to the induction of anaesthesia, of each patient's name, age, sex and weight. The time from commencement of induction of anaesthesia to completion of the eye dressing (the duration of anaesthesia) was noted. A record was made of each patient's heart rate (HR), systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressure on 12 occasions in the peri-operative period. These data were transcribed from the printout produced by the automatic blood pressure device (1) 60 s prior to induction of anaesthesia (base-line values), (2) 60 s after topical laryngeal spray with lignocaine, (3) 1, 2, 3, 4 and 5 min following endotracheal intubation, (4) at 15, 30 and 45 min intra-operatively, (5) on completion of surgery and application of the eye dressing, but prior to reversal of residual neuromuscular blockade, and (6) 60 s following extubation. Finally, a note was made during surgery of each instance when atropine, labetalol or ephedrine was required to maintain the HR and SAP at the defined levels. The eye bandage was applied by the surgeon and comprised chloromycetin eye ointment applied to the conjunctiva, sofratulle and an eye pad laid over the closed lids; an eye shield was placed over the dressing and fixed firmly to the patient's face using micropore adhesive tape.

Statistical analysis

Patient data were analysed using Fisher's Exact test and one-way analysis of variance (Anova). The incidences of rescue drug requirements for healthy and diseased patients in each test group and overall were compared using Fisher's Exact test.

The area under the time curve (AUC) for HR, SAP, DAP and MAP for each patient was computed using the trapezoidal rule. Comparisons of these variables between healthy and diseased patients in each test drug group were made using one-way Anova and between test drug groups using two-way Anova. Comparisons between drug groups were made using the technique of Scheffe [28] to test for significant differences.

Changes in haemodynamic variables within each drug group associated with laryngoscopy laryngeal spraying and laryngoscopy/intubation were compared with pre-induction values using paired Student's t-tests. The same analysis was used to test for differences in these variables between the means of these values recorded at the 45th min of surgery and those recorded after application of the eye bandage and after extubation.

Statistical difference were considered significant if P<0.05.

Results

Comparison of patient data

One hundred consecutive patients (healthy n=52, diseased n=48) presenting for cataract extraction under general anaesthesia at this hospital between January and December 1993 were studied. This study population comprised five groups of 20 ASA Grade I to III middle-aged to elderly patients. The groups were comparable with respect to sex, age, body weight, duration of anaesthesia, health and disease (Table 1). Of those given magnesium sulphate, one 85-year-old male suffering from hypertension and ischaemic heart disease developed ventricular bigeminy following the induction of anaesthesia: the dysrhythmia was treated with i.v. lignocaine. This patient was excluded from the study, and replaced by the subsequent male patient presenting for surgery. The end-operative data on one patient given i.v. lignocaine as test medication were inadvertently not recorded; the ten sets of data from the pre-induction period to the 45th min of surgery on this patient were, however, entered into the data bank.

Table 1
Table 1:
Demographic data (I) healthy, diseased patients and total study population given saline (S), magnesium sulphate (M), esmolol (E), lignocaine (L) or glyceryl trinitrate (G)

The 48 patients suffering from ischaemic heart disease, diabetes, hypertension or any combination of these diseases were stabilized on one or more of a variety of medications pre-operatively. Their medications included cardioactive drugs, beta-adrenoreceptor antagonists, other anti-hypertensive drugs, insulin or oral hypoglycaemics (Table 2). All patients were deemed to be in optimal health to undergo cataract surgery under general anaesthesia.

Table 2
Table 2:
Demographic data (II): numbers of healthy and diseased patients and their nature of treatment

Comparisons of haemodynamic responses of healthy and diseased patients

For each variable (HR, SAP, DAP, MAP) there were three significant differences (Anova) between healthy patients and those suffering from one or more of diabetes, hypertension or ischaemic heart disease within each drug group. These differences occurred in comparisons of the systolic blood pressures of normal and diseased patients given lignocaine i.v. and of systolic and diastolic blood pressures of those given GTN (Table 3). However, overall there were no significant differences (Anova) between the cardiovascular responses of the 52-healthy and the 48-diseased patients studied. (Tables 3–5; Fig. 1 and 2).

Table 3
Table 3:
Comparisons of data for normal and diseased patients in each test drug group using analysis of variance and comparing areas under the curve (F-values from one-way analyses of variance are shown)
Table 4
Table 4:
Comparison of haemodynamic responses of healthy and diseased patients using analysis of variance (95% least significant difference) and comparing areas under the curve (AUC) analysis by one-way Anova; all comparisons non significant; data given as mean (standard error of the mean, SEM)
Table 5
Table 5:
Comparison of heart rates and mean blood pressures (mean [standard deviation]) of normal and diseased patients from start to end of anaesthesia
Fig. 1.
Fig. 1.:
Peroperative heart rates and mean blood pressures of normal and diseased patients.
Fig. 2.
Fig. 2.:
Comparison of haemodynamic rsesponses of healthy (H) and diseased (D) patients using analysis of variance (95% least significant difference) and comparing areas under the curve. Analysis by two-way Anova; all comparisons not significant; data given as mean: standard error of the mean.

The requirements for rescue drugs (atropine, labetalol and ephedrine) by healthy and diseased patients within each test drug group and overall were similar (Table 6). Atropine and labetalol were administered infrequently (in 12 and 13%, and in 6 and 8% of patients respectively), but ephedrine was required very frequently (in 62 and 65% of patients respectively).

Table 6
Table 6:
Intra-operative requirements of rescue drugs by healthy and diseased patients in all test drug groups

Effects of test drugs on haemodynamic responses to peroperative noxious stimuli

Differences between the effects of the test drugs on heart rate and blood pressures were only evident until about 5 min following tracheal intubation. During surgery, any deviations in haemodynamic variables from the defined levels were corrected using the appropriate rescue drugs. At the end of surgery there were no differences in the chronotropic and pressor responses to eye dressing and extubation between the groups (Fig. 3). The means (standard deviations) of HR, SAP, DAP and MAP within each drug group at each of the 12 occasions of measurement are presented in Table 7.

Fig. 3.
Fig. 3.:
Peroperative cardiovascular charts.
Table 7
Table 7:
Peroperative heart rates and blood pressures (mean [standard deviation]) of patients given saline (placebo), magnesium sulphate (MgSO4), esmolol, lignocaine (ligno) and glyceryl trinitrate (GTN)

Heart rate (HR). Laryngoscopy and topical lignocaine spray produced significant rises in HR (P<0.001, paired Student's t-tests) of between 12 and 18 beats min−1 in all except the esmolol group. This rise was maintained or increased by endotracheal intubation but had resolved to base-line levels by the 3rd to 4th min after intubation (Fig. 3). During surgery, until the 45th min, a gradual slowing of HR occurred in all groups. Application of the eye bandage then caused a slight but non-significant rise in HR (paired Student's t-tests, all drugs) similar to the initial increase after intubation in all groups.

Comparisons between the effects of the pairs of drugs (Scheffe's Method) on the AUC for HR over the whole study period revealed significant differences only between (1) saline and lignocaine, and (2) esmolol and lignocaine (Fig. 4).

Fig. 4.
Fig. 4.:
Comparison between the effects of saline (S), magnesium sulphate (M), esmolol (E), lignocaine (L) and glyceryl trinitrate (G) on haemodynamic responses to peroperative stimuli using analysis of variance (95% least significant difference) and comparing areas under the curve using the technique of Scheffe. Data given as mean: standard error of the mean.

Systolic arterial pressure (SAP). Laryngoscopy and the application of aerosolized lignocaine to the upper airway produced no changes in SAP in those patients given saline, magnesium sulphate or lignocaine. However, subsequent laryngoscopy and tracheal intubation produced significant rises (P<0.001 all comparisons, paired Student's t-tests) of between 11 and 28 mmHg in these groups. Conversely, highly significant falls (P<0.001 both comparisons, paired Student's t-tests) of between 43 and 41 mmHg were observed in patients receiving esmolol and GTN, respectively, following induction of anaesthesia, laryngoscopy and topical lignocaine spray. Tracheal intubation then produced increases, within 1 to 2 min, in SAP of these two groups to mean values which were similar (paired Student's t-tests) to their respective pre-induction base-line pressures (Fig. 3). However, comparisons between the effects of the individual drugs (Scheffe) on the AUC over the whole study period revealed differences only between the effects of magnesium sulphate and glyceryl trinitrate (Fig. 4). During surgery mean SAP was maintained at similar levels in all groups by the use of ephedrine and labetalol. Application of the eye bandage produced significant increases in SAP (P<0.001, all comparisons, paired Student's t-tests) to above base-line levels in all groups. Extubation was associated with significant rise in SAP in all groups of similar magnitudes (paired Student's t-tests) to those seen following tracheal intubation in patients given saline, lignocaine and magnesium sulphate (Fig. 3).

Diastolic arterial pressure (DAP). In those patients given saline and i.v. lignocaine, DAP increased following laryngoscopy and spraying of the upper airway with lignocaine (P<0.05, both comparisons, paired Student's t-tests) and following laryngoscopy with endotracheal intubation (P<0.001, both comparisons, paired Student's t-tests), but remained similar to base-line levels in patients given magnesium sulphate, esmolol and glyceryl trinitrate. However, comparisons between the effects of the individual drugs on DAP (Scheffe) over the whole study period revealed no inter-drug differences (Table 4). During surgery there were gradual reductions in DAP in all groups followed by a significant rise (P<0.001, all comparisons, paired Student's t-tests) to base-line levels on application of the eye dressing. Further rises to above base-line levels then occurred in all groups after extubation (Fig. 3).

Mean arterial pressure (MAP). In those patients given saline and i.v. lignocaine the MAP increased following laryngoscopy with laryngeal spraying (P<0.05, both comparisons, paired Student's t-tests) and following laryngoscopy with endotracheal intubation (P<0.001, both comparisons, paired Student's t-tests). The MAP remained unchanged in those patients given magnesium sulphate prior to these procedures, but fell significantly (P<0.01, both comparisons, paired Student's t-tests) following laryngeal spraying in those patients given. esmolol and glyceryl trinitrate. In the latter two drug groups the stimulus of tracheal intubation produced a rise in MAP to base-line levels. During subsequent anaesthesia gradual reductions in MAP occurred in all groups followed by a significant rise (P<0.001, all comparisons, paired Student's t-tests) to base-line levels on application of the eye bandage. A further significant rise (P<0.001, all comparisons, paired Student's t-tests) to above base-line levels occurred following extubation (Fig. 3). However, comparisons of the effects on MAP of the individual drugs (Scheffe) throughout the study period revealed no inter-drug differences during each laryngoscopy and endotracheal intubation (Fig. 4).

Rate pressure product (RPP). The stimuli of laryngoscopy/laryngeal spraying and laryngoscopy/tracheal intubation produced stepwise rises in the RPP in all drug groups except those patients given esmolol. These rises in RPP were for saline 11 174 (SD2529)—14 378 (SD6899)—17 005 (SD4400); magnesium sulphate 12 897 (SD3611)—14 043 (SD4538)—15 640 (SD5057); lignocaine 13 202 (SD3238)—16 038 (SD6837)—17 978 (SD8154) and glyceryl trinitrate 11 026 (SD2548)—11 682 (SD5415)—13 095 (SD6412). During subsequent anaesthesia the RPP in all drug groups was maintained at similar levels by the use of rescue drugs. In all drug groups, application of the eye bandage produced rises in RPP to >12 000, and tracheal extubation induced further rises in RPP to >17 000 (Fig. 3).

Pressure rate quotient (PRQ). The initial PRQ in all groups was between 1.4 and 1.5. The PRQ remained >1.0 in all groups throughout the peri-operative period with the exception of those given glyceryl trinitrate. In this group the PRQ fell to <1.0 following laryngoscopy with spraying of the larynx, with increased to >1.0 following tracheal intubation (Fig. 3).

Discussion

This study compared the effects of magnesium sulphate, esmolol, lignocaine, glyceryl trinitrate and placebo given i.v. during the induction of anaesthesia on the haemodynamic responses to topical laryngeal spraying with lignocaine, tracheal intubation, surgery and anaesthesia, eye bandaging and tracheal extubation in healthy and diseased patients undergoing cataract extraction. Recordings were not made after induction but prior to laryngeal spray as the study was not designed to investigate the haemodynamic effects of the test drugs unaffected by laryngoscopy and intubation. This omission in the design of the study is regrettable as knowledge of the separate effects of induction, test drugs and spray would have been valuable. However, patients were given the same balanced general inhalational anaesthetic drugs which is believed to be suitable for this type of surgery. Since the haemodynamic responses to tracheal intubation are short-lived, short-acting anti-hypertensive drugs (such as esmolol and sodium nitroprusside) may be most appropriate to attenuate them. Those studies of the longer acting drugs (such as lignocaine and magnesium sulphate) used to attenuate these responses [11,19] give no indication of their residual cardiovascular effects during subsequent anaesthesia and, of special interest, during extubation.

Exaggerated responses to laryngoscopy and intubation have been demonstrated in diabetic [29] and hypertensive [30] patients, though studies on this phenomenon usually exclude patients with cardiovascular disease [9]. The report on the effects of diabetic autonomic dysfunction on the cardiovascular responses to induction of anaesthesia and tracheal intubation [29] was published during this investigation, and hence autonomic dysfunction in diabetics was not taken into account in this study. Also, though the RPP as an indicator of myocardial ischaemia is controversial [7,8], these data are presented for completeness sake. Many of the elderly patients submitted for cataract extraction under general anaesthesia are apprehensive at the prospect of anaesthesia. This anxiety was manifest by high preinduction SAPs in all the test groups, and by RPPs in excess of 12 000 in the saline and lignocaine groups, despite premedication with temazepam. However, no patient complained of angina or manifested ECG changes suggestive of myocardial ischaemia during this time. This study demonstrated, surprisingly, that the haemodynamic responses of healthy middle-aged to elderly patients and those with co-existing treated hypertension, diabetes, ischaemic heart disease or a combination of these diseases are similar during anaesthesia. The expectation that those with these diseases would show cardiovascular lability was not realized.

During the peroperative period each patient was exposed to six sources of noxious stimuli; induction anaesthetic and test drugs, laryngoscopy and topical spray of lignocaine to the upper airway, repeat laryngoscopy and tracheal intubation, surgical manipulations during anaesthesia, eye bandaging and, finally, pharyngeal suction and tracheal extubation. However, differences attributable to the test drugs were only evident during and until about 5 min after the induction of anaesthesia and placement of the tracheal tube.

In patients given saline, the stimuli during the induction of anaesthesia and at the end of surgery and anaesthesia produced marked chronotropic and pressor responses. Only esmolol (given i.v. 4.45±1.03 min prior to intubation) attenuated the tachycardia and hypertension caused by laryngoscopy and intubation, and yielded RPP and PRQ indices which reduce the likelihood of myocardial ischaemia [4,6–8]. Glyceryl trinitrate (given i.v. 5.75±0.89 min prior to intubation) ameliorated the pressor response to intubation, but was associated with tachycardia, RPP and PRQ indices immediately following laryngoscopy and intubation which may increase the likelihood of myocardial ischaemia [4,6–8]. Magnesium sulphate and lignocaine (given i.v. 4.35±1.34 and 4.69±0.94 min respectively prior to intubation) did not attenuate either the chronotropic or the pressor responses to laryngoscopy and intubation, findings which contradict reports claiming such efficacy [19,23].

The observation that laryngoscopy and the topical application of lignocaine caused pronounced tachycardia in all the test groups except those given esmolol suggests that the vasomotor response to laryngoscopy per se manifests predominantly as a chronotropic response. The observation that blood pressures were maintained at base-line levels 1 min following laryngoscopy and the application of aerosolised lignocaine to the upper airway in the saline, lignocaine and magnesium sulphate groups of patients suggests, further, that the pressor effect of laryngoscopy is masked by the hypotensive effects of the drugs given to induce anaesthesia. The maintained tachycardia and rise in BP following tracheal intubation through an upper airway anaesthetized with topical lignocaine confirms that topical lignocaine does not prevent the sympathoadrenal responses to repeat laryngoscopy and tracheal intubation [31–33]. We have now abandoned its use. The recording of very low blood pressure after the application of aerosolized lignocaine in the esmolol and GTN groups suggests that topical application of lignociane is contraindicated when using either esmolol or glyceryl trinitrate to attenuate the pressor response to subsequent intubation. The pressor response to laryngoscopy per se appears to be insufficient to counteract the combined hypotensive effects of anaesthetic induction drugs and either esmolol or GTN.

The pressure exerted on the eye during application of the eye bandage produced marked vasomotor responses, an observation which is consistent with reports which link ocular manipulation and cardiovascular morbidity [34–36]. Further increases in HR, BP and RPP occurred in all the drug groups following extubation. These findings illustrate the severity of this response in elderly patients and, of especial interest, reveal that none of the test drugs given during induction of anaesthesia have a protective effect at the end of surgery (some 75 min later).

Ten observations are drawn from this study. (1) Middle-aged to elderly healthy patients and those being treated for hypertension, diabetes, ischaemic heart disease or a combination of these diseases demonstrate similar haemodynamic responses to the various anaesthetic and surgical stimuli inflicted during routine cataract surgery performed under balanced inhalational general anaesthesia. (2) Esmolol alone attenuates both the rise in HR and arterial pressure associated with laryngoscopy and tracheal intubation, and maintains satisfactory RPP and PRQ indices during this time. (3) GTN attenuates the pressor responses to laryngoscopy and intubation, but is associated with pronounced chronotropic, RPP and PRQ changes during this period. (4) Magnesium sulphate and lignocaine provide no protection, under the conditions of this study, against the cardiovascular responses to laryngoscopy and tracheal intubation. (5) The application of aerosolized lignocaine to the upper airway does not attenuate haemodynamic responses to subsequent tracheal intubation, and appears to be associated with pronounced hypotension if esmolol or glyceryl trinitrate have been given to attenuate the former responses. (6) The stimulus of laryngoscopy and application of topical lignocaine to the upper airway manifests as a less profound vasomotor response than does the subsequent stimulus of laryngoscopy and endotracheal intubation under the dynamic conditions pertaining during induction and intubation. (7) The effects of magnesium sulphate, esmolol, lignocaine and glyceryl trinitrate given at induction of anaesthesia are only evident for about 5 min following tracheal intubation, and have no demonstrable cardiovascular effects during subsequent anaesthesia and surgery, eye bandaging and, ultimately, tracheal extubation. (8) Application of the eye dressing causes rises in HR and BP, which are augmented by extubation. (9) The pronounced chronotropic and pressor responses induced by extubation suggest that esmolol, in an optimal dose still to be determined for geriatric patients, should be given i.v. prior to extubation. (10) Finally, the omission of post-induction pre-laryngeal spray recordings of all variables does not allow an assessment of the haemodynamic effect of these drugs unaffected by laryngoscopy and intubation, an investigation which remains to be undertaken.

Acknowledgments

The authors are deeply indebted to Drs A. El Eiffan, S. Al Saleh and A. Faqeeh (Consultant Ophthalmologists) for permission to study their parents, Mary Crickard (Librarian), Irene Beirne and Patricia Boylan (Anaesthesia Secretaries), Colin McNicoll and Derek Fyfield (Computer Graphics), Bob Ashford and Steve Nally (Medical Illustration) and Professor D. Price-Evans and Dr P. Riley (Statistics and proof reading) for their combined contributions to this project.

References

1 Siedlecki J. Disturbances in the function of cardiovascular system in patients following endotracheal intubation and attempts at their prevention by pharmacological blockade of the sympathetic system. Anaesth Resusc Inten Ther 1975; 3: 107–110.
2 Bidwai AR, Bidwai VA, Rodgers CR et al. Blood pressure and pulse-rate responses to endotracheal extubation with and without prior injection of lignocaine. Anesthesiology 1979; 51: 171–173.
3 Guyton AC. Cardiac output, venous return and their regulation. Textbook of Medical Physiology, 8th Edn. Philadelphia: W.B. Saunders Co., 1991; 221–254.
4 Slogoff S, Keats AS. Does perioperative myocardial ischemia lead to postoperative myocardial infarction? Anesthesiology 1985; 62: 107–114.
5 Fox EJ, Sklar GS, Hill CH et al. Complications related to the pressor response to endotracheal intubation. Anesthesiology 1977; 47: 524–525.
6 Buffington CW. Haemodynamic determinants of ischemic myocardial dysfunction in the presence of coronary stenosis in dogs. Anesthesiology 1985; 63: 651–662.
7 Urban MK, Gordon MA, Harris SN et al. Intraoperative haemodynamic changes are not good indicators of myocardial ischemic. Anesth Analg 1993; 76: 942–949.
8 Shiraki H, Lee S, Yong WH et al. Diagnosis of myocardial ischemia by the pressure-rate quotient and diastolic time interval during coronary artery bypass surgery. J Cardiothorac Anesth 1989; 3: 592–596.
9 Helfman SM, Gold MI, Delisser EA et al. Which drug prevents tachycardia and hypertension associated with tracheal intubation: lidocaine, fentanyl or esmolol? Anesth Analg 1991; 72: 482–486.
10 Stoelting RK. Circulatory responses to laryngoscopy and tracheal intubation with or without prior oropharyngeal viscous lidocaine. Anesth Anal 1977; 56: 618–621.
11 Tam S, Chung F, Campbell M. Intravenous lidocaine: optimal time of injection before tracheal intubation. Anesth Analg 1987; 66: 103–108.
12 Chung F, Evans D. Low dose fentanyl: haemodynamic responses during induction and intubation in geriatric patients. Can Anaesth Soc J 1985; 26: 622–628.
13 Black TE, Kay B, Healy TEJ. Reducing the haemodynamic responses to laryngoscopy and intubation. A comparison of alfentanil with fentanyl. Anesthesia 1984; 39: 883–887.
14 Stoelting RK. Attenuation of blood pressure response to laryngoscopy and tracheal intubation with sodium nitroprusside. Anesth Analg 1979; 58: 116–119.
15 Mahajaran RP, Ramachandran R, Saxena N. Topical nitroglycerine prevents the pressor response to tracheal intubation and sternotomy in patients undergoing coronary artery bypass graft surgery. Anesthesia 1993; 48: 297–300.
16 Maekawa N, Mikawa K, Nishina K et al. Attenuation of the pressor response to tracheal intubation with oral nitrendipine. Acta Anaesthesiol Scand 1993; 38: 668–671.
17 Kale SC, Mahajaran RP, Jayalakshami TS et al. Nifedipine prevents the pressor response to laryngoscopy and tracheal intubation in patients with coronary artery disease. Anesthesia 1988; 43: 495–497.
18 Pouttu J, Sheinin P, Rosenberg PH et al. Oral premedication with clonidine: effects on stress responses during general anaesthesia. Acta Anaesthesiol Scand 1987; 31: 370–374.
19 James MFM, ErykBeer R, Esser JD. Intravenous magnesium sulfate inhibits catecholamine release associated with tracheal intubation. Anesth Analg 1989; 68: 772–776.
20 McCarthy GJ, Hainsworth M, Lindsay K et al. Pressor responses to tracheal intubation after sub-lingual captopril. A pilot study. Anaesthesia 1990; 45: 243–245.
21 Micromedex, Inc. 1974–1994. Volume 90. Drug Evaluation Monograph: Nitroglycerine. In: Computerized Information Services for Medicine and Industry. Denver, Co, USA.
22 Reynolds JEF (ed). Martindale The Extra Pharmacopoeia 29th Edn. London: The Pharmaceutical Press, 1989: 788, 1499–1502.
23 Splinter WM, Cervenko F. Haemodynamic responses to laryngoscopy and tracheal intubation in geriatric patients: effects of fentanyl, lidocaine and thiopentone. Can J Anaesth 1989; 36: 370–376.
24 James MFM. Use of magnesium sulphate in the anaesthetic management of phaeochromocytoma: a review of 17 anaesthetics. Br J Anaesth 1989; 62: 616–623.
25 Sheppard S, Eagle CJ, Strunin L. A bolus dose of esmolol attenuates tachycardia and hypertension after tracheal intubation. Can J Anaesth 1990; 37: 202–205.
26 van den Berg AA, Lambourne A. Prochlorperazine and vomiting after eye surgery. Anaesthesia 1987; 42: 898.
27 van den Berg AA. ENT and eye anaesthesia. To spray or not to spray—a rationalisation. Anaesthesia 1993; 48: 742.
28 Scheffe H. A method of judging all contrasts in the analysis of variance. Biometnika 1953; 40: 87–104.
29 Vohra A, Kumar S, Charlton AJ et al. Effect of diabetes mellitus on the cardiovascular responses to induction of anaesthesia and tracheal intubation. Br J Anaesth 1993; 71: 258–261.
30 Low JM, Harvey JT, Prys Roberts C et al. Studies of anaesthesia in relation to hypertension. VII. Adrenergic responses to laryngoscopy. Br J Anaesth 1986; 58: 471–477.
31 Wilson IG, Meiklejohn BH, Smith G. Intravenous lignocaine and sympathoadrenal responses to laryngoscopy and intubation. The effect of varying time of injection. Anaesthesia 1991; 46: 177–180.
32 Derbyshire DG, Smith G, Achola KJ. Effect of topical lignocaine on the sympathoadrenal responses to tracheal intubation. Br J Anaesth 1987; 59: 300–304.
33 Laurito CE, Baughman VL, Becker GL et al. Effects of aerolized and/or intravenous lidocaine on hemodynamic responses to laryngoscopy and intubation in outpatients. Anesth Analg 1988; 67: 389–392.
34 Aschner B. Ueber einen bisher noch nicht beschriebenen reflex vom auge auf krieslauf und atmung. Verschwinden des radialispulsis bei druck auf, des auge. Wiener Klinische Wochenschrift 1908; 21: 1529–1530.
35 Shanks AB, O'Carroll TM. Oculocardiac reflex from the empty orbit. Anaesthesia 1984; 39: 291.
36 Arnadt GA, Stock MC. Bradycardia during cold ocular irrigation under general anaesthesia: an example of the diving reflex. Can J Anaesth 1993; 40: 511–514.
Keywords:

Surgery, cataract extraction; Anaesthesia, general, tracheal intubation, extubation; Complications, heart rate, blood pressure, rate-pressure product, pressure-rate quotient; Drugs, magnesium sulphate, esmolol, glyceryltrinitrate, lignocaine, saline

© 1997 European Academy of Anaesthesiology