Esmolol blunts the haemodynamic responses to tracheal intubation in treated hypertensive patients

778

Esmolol blunts the haemodynamic responses to trache, al intubation in treated hypertensive patients

Suman Sharma MD, Sukanya Mitra MD, Vinod Kumar Grover MD MNAMS, Rashmi Kalra MD

Purpose: To compare the ability of different bolus doses of

esmolol to blunt the haemodynamic effects of laryngoscopy

and tracheal intubation in treated hypertensive patients.

Methods: In this randomised, double-blind placebo controlled

study, 45 ASA I1 patients, treated .for essential hypertension

with drugs other than beta blockers, were divided into three

groups" of 15 patients each. Patients in different groups either

received 20 ml normal saline (Group P), or I00 mg esmolol

(Group Eioo) or 200 mg esmolol (Gro,tp E2oo) as a single bolus

intravenous dose before laryngoscopy and intubation. Systolic,

diastolic and mean arterial pressure and heart rate were mon-

itored for up to I0 rain following intubation and were com-

pared with respective basal readings as well as across groups.

Resultx: Esmolol alone reduced systolic arterial pressure (P <

0.01 in Group Eto o and P < 0.001 in Group E2oo) and heart rate (P < 0.001). Though there was an increase in arterial pressure and heart rate in the control group, esmolol 100 mg

maintained arterial pressure and heart rate at levels compara-

ble to basal values throughout the study (P > 0.05). Patients

receiving esmolol 200 mg had lower values (P < 0.001) than

their basal readings during most of the post-intubation study

period.

Conclusion: Esmolol I00 mg given as bolus, is effective as

well as safe in blunting the haemodynamic responses to laryn-

Key words COMPLICATIONS: hypertension; INTUBATION, TRACHEAL: complications, haemodynamic

response; SYMPATHETIC NERVOUS SYSTEM: beta adrenergic

antagonist, esmolol.

From the Department of Anaesthesia, Postgraduate Institute of Medical Education and Research, Chandigarh- 160012, India.

Address Correspondence to: Dr. S. Sharma, Department of Anaesthesia, Postgraduate Institute of Medical Education and Research, Chandigarh- 160012, India.

Phone: (0172)-545075. Fax: 541401. Accepted for publication 30th March, 1996.

goscopy and tracheal intubation in treated hypertensive

patients.

Objectif" Comparer l'efficacit~ de diff~;rentes doses d'esmolol

administrdes pour attdnuer les effiets h~modynamiques de la

laryngoscopie et de l'intubation de la trachde chez des hyper-

tendus traitds.

M~thodes: Dans cette gtude contrOlde aldatoire, gt double

aveugle avec placebo, 45 patients ASA IL traitds pour hyper-

tension essentielle avec des m6dicaments autres que des [3-blo-

quants ont dtg rdpartis en trois groupes de 15 patients, lls ont

re~:u soit 20 ml de sol. physiologique (groupe P), soit I00 mg

d'esmolol (groupe Etoo), soit 200 mg d'esmolol (groupe E2oo)

en un seul bolus intraveineux avant la laD,ngoscopie et l'intu-

bation. Les pressions systolique, diastolique et moyenne ainsi

que la frdquence cardiaque ont dtd monitords pendant I0 rain aprbs l'intubation et compardes aux mesures initiales et entre

les groupes.

Rdsultats: Seul l 'esmolol a diminu# la pression artgrieUe sys-

tolique (P < 0,01 dans le groupe Ejoo et P < 0,001 dans le

groupe E2oo) et la .frdq,~ence cardiaque (P < 0,001). Alors qu 'on notait une augmentation de la pression art6rielle et de

la fr~;quence cardiaque dans le groul)e contrg)le, l'esmolol

I00 mg maintenait la pression artdrielle et la .frdquence

cardiaque h des niveaux comparables aux valeurs initiales

(P < 0,05). Les patients recevant esmolol 200 mg avaient des

valeurs infdrieures (P < 0,001) aux valeurs initiales pendunt

la majeure partie de la pdriode dtudi~e.

Conclusion: L'esmolol 100 mg administrd en bolus est effi- (:ace et sans danger pour attdnuer les r~ponses hdmody-

namiques de la laryngoscopie et de l'intubation chez des

hypertendus trait~s.

Laryngoscopy and tracheal intubation are noxious stimuli that produce marked sympathetic response manifest- ing as hypertension and tachycardia. I In susceptible individuals, especially those with systemic hypertension, coronary artery disease, cerebrovascular disease and intracranial aneurysm, the effect of this transient

CAN J ANAESTH 1996 / 43:8 / pp778-82

Sharma et al.: ESMOLOL AND HYPERTENSION 779

sympathetic response can evoke life threatening condi- tions. 2 Herein lies the rationale to continue the quest for an anaesthetic technique where the cardiovascular effects of these stimuli could be attenuated.

Reflex tachycardia and hypertension during laryngoscopy and intubation are old problems encountered by anaesthetists. 3 The responses are exaggerated in both treated and untreated hypertensive patients. 4 Therefore, anaesthetists have been trying to obtund these untoward reflexes by the use of various agents. 5-~3 Esmolol, a water soluble selective beta adrenoceptor antagonist is one such drug. It has a rapid onset and ultra-short duration of action with a half life of nine minutes. 14 The pharmacological properties of rapid onset and offset of action of this drug are particularly advantageous during anaesthesia in obtunding the haemodynamic stress response. ~4-t6 There are no reports on the efficacy of esmolol in blunting the pressor response to tracheal intubation in patients with systemic hypertension, who constitute a high-risk group for developing adverse cardiovascular consequences of laryngoscopy and intubation. 2.4 This prompted us to study the effect of this drug in attenuating pressor responses in hypertensive patients treated with non beta-blocker drugs.

Methods The protocol was approved by the Institute Ethics Committee. The procedure was explained to the patients who gave informed consent. Forty-five ASA class II adult patients with mild to moderate essential hypertension, receiving antihypertensive treatment with non-beta blocking agents or diuretics, booked for elective abdom- inal surgery were studied. Patients having a heart rate <70 bpm, systolic blood pressure <120 mmHg, chronic obstructive lung disease (especially bronchial asthma), past history of angina or myocardial infarction in last three months, heart blocks and congestive cardiac failure were excluded from the study. They were randomly allocated into three groups of 15. All patients received 20 ml solution iv in a double blind manner. Group P received 20 ml normal saline, Group E~0o received 100 mg esmolol and Group E200 received 200 mg esmolol in 20 ml of normal saline.

All patients received premedication with diazepam 10 mg p o on the night before surgery and 5 mg on the morning of surgery, followed by 0.15 mg .kg -~ mor- phine and 0.4 mg.kg -I promethazine im one hour before anaesthesia. Patients received their oral antihypertensive medication two hours before anaesthesia.

All patients were transferred to the operating theatre and, after ten minutes, were connected to a non'-invasive blood pressure (NIBP) monitor and ECG. Depending on their group allocation patients received 20 ml normal

TABLE 1 Background data of the three groups: placebo (Group P), esmolol 100 mg (Group Et(~) and esmolol 200 mg (Group E20~)). (Mean _ SEM)

Group P Group Etoo Group E2oo n= 15 n= 15 n= 15

Age yr 50.8 • 1.2 54.9 • 1.6 56.6 • 2.0 Weight kg 75.7 • 69. I • 2.2 73.5 • Male:Female 5:1 4:11 5:10 Heart Rate bpm 89.0 -+ 1.9 89.5 • 3.0 93.1 • 2.8 SAP mmHg 158.9 _+ 2.8 163.0 • 2.6 159.7 _ 1.9 DAP mmHg 102.7 • 1.0 102.5 • 1.0 102.3 • 1.0

SAP - systolic arterial pressure; DAP - diastolic arterial pressure.

saline (Group P), esmolol 100 mg in 20 ml of saline (Group E~oo), or esmolol 200 mg in 20 ml of saline (Group E20o) as a bolus over five seconds. One minute later anaesthesia was induced with 5 mg kg -~ thiopentone, tollowed by 2 mg kg -I succinylcholine. Laryngo- scopy and tracheal intubation were performed after the onset of apnoea. Time from administration of esmolol to tracheal intubation was approximately two minutes. Patients were excluded from the study if there was diffi- culty in intubation, or multiple attempts were required. Following intubation, the lungs were ventilated, after connection to a Bain's circuit, with 66% nitrous oxide in oxygen. For the next ten minutes, systolic, diastolic and mean arterial blood pressure (MAP), heart rate and ECG changes were measured at one minute after the administration of esmolol or saline (Pt), at laryngoscopy and intubation (time 0) and at I, 3, 5, 7 and 10 min there- after. All surgical stimuli, analgesic supplements and inhalational anaesthetics were avoided during the study.

The data collected were analysed using one way analysis of variance (ANOVA) for intergroup comparisons, and paired ' t ' tests for comparing scores at various time intervals within each group. For the latter, Bonferroni correction was applied since it was decided beforehand that the multiple comparisons would be made against the baseline measure only (seven comparisons in each set). The results were considered signifi- cant when P < 0.05.

Results The patients in the three groups were comparable with respect to age, body weight and sex (Table I). In Group P, there was no change in MAP one minute after 20 ml saline, while after thiopentone and at laryngoscopy there was a decrease in MAP (P < 0.001). Following laryngoscopy and intubation there were an increase in MAP at one, three, five and seven minutes after intubation (P < 0.001). At ten minutes it was comparable to the basal value (P > 0.05). In Group Ei0o, there was a decrease in

780 CANADIAN JOURNAL OF ANAESTHESIA

TABLE II Mean arterial pressure (mmHg) in the three groups:placebo (Group P), esmolol 100 mg (Group El00) and esmolol 200 mg (Group E~0o).

Group P Group Eto o Group E2oo l ime n = 1 5 n = 1 5 n = 1 5

Basal 111.4 + 0.9 108.8 • 1.4 1119.5 • 0.9 PI 111.6 • 0.9 104.5 • 1.31":[: 97.9 • 1.4"t" 0 106.7 • 0.8* 107.0 • 1.2:1: 99.2 • 1.8*t I 132.0• 107.3 • 0.8t.~ 100.0 • 2.1*t 3 130.0 • 1.8" 107.0 • 1.2"1":1: 102.2 • 1.6"1" 5 1123.9+ 1.3" 106.8• 1.2t 13.3 • 1.8t 7 118.7 • 1.0" 107.0 • 1.2t 104.1-• 1.7"I"

10 113.1 • 107.3• 1.3t 105.4• 1.6t

Note: all values represent mean (mmHg) • SEM. Time PI denotes one minute after pre-treatment (with esmolol or saline). *Difference from respective basal value P < 0.05 after applying Bonferroni correction. tDifference from respective Group P value P < 0.05. ~Difference from respective Group F_a0 . value P < 0.05.

TABLE IV Diastolic arterial pressure (mmHg) in the three groups: with placebo (Group P), esmolol 100 mg (Group Eioo) and esmolol 200 mg (Group E20o)

Group P Group Eioo Group E2oo Time n= 15 n = 15 n =15

Basal 92.6 • 1.0 89.3 • 1.4 90.2 • 0.9 PI 92.4 • 0.9 86.5 • 1.21":1: 82.4 • 1.4*t 0 86.5 -+ 0.8* 88.0 • 1.6~- 83.0 • 1.8*t 1 111.5_+2.5' 89.1 • 1.01" 83.6• 1.8*t 3 110.5• 87.6• 1.3t 85.1 • 1.4*t 5 104.3• 1.6" 87.8• l . l t 97.5• 1.6t 7 99.6• 1.4' 87.8• 1.1.t" 97.5• 1.6t

10 94.3 • 0.9 88.4 • 1.2? 87.8 • 1.7t

Note : all values represent mean (in mm Hg) • SEM. Time PI den6tes I min after pre-treatment (with esmolol or saline). * Difference from respective basal value at P < 0.05 after Bonferroni correction. ? Difference from respective Group P P < 0.05. :~ Difference from respective Group E20 o at P < 0.05 or lesser.

TABLE Ill Systolic arterial pressure (mmHg) in the three groups: placebo (Group P), esmolol 100 mg (Group Eico) and esmolol 200 mg (Group E20o)

Group P Group Ewo Group E2o o Time n = 1 5 n = 15 n = 1 5

Basal 149.3 • 2.1 148.1 • 2.5 147.4 • 1.7 PI 150.3• 141.6 • 2.3~:i: 129.2 • 2.3"$ 0 142.9• I/9" 144.6+ 1.8~t 131.7 • 2 .5 ' t 1 173.2 • 3.2* 146.6 • 1.6t:i: 133.7 • 3.0"$ 3 170.7• 146.2 • 1.91":i: 136.7 _+ 2.3'$ 5 163.6• 1.7" 146.2• 1.9t:]: 137.7 • 2.3t 7 157.2• 1.4" 144.2 • 2. I-r:[: 137.9 • 2.4t

10 151.0 • 1.9 144.8 • 2.6-r 140.4 • 1.8t

Note: all values represent mean (mmHg) • SEM. Time P1 denotes 1 min after pre-treatment (with esmolol or saline). *Difference from respective basal value P < 0.05 after Bonferroni correction. tDifference from respective Group P value P < 0.05 :i:Difference from respective Group E2t~) value P < 0.05.

M A P f o l l o w i n g in jec t ion o f e s m o l o l (P < 0.01). Af te r

t h i o p e n t o n e and l a r y n g o s c o p y the inc rease in in M A P

was not s ta t i s t ica l ly s ign i f i can t and the rea f te r t h rough-

ou t the s tudy per iod the M A P va lues r e m a i n e d s tab le ( P

> 0.05).

In G r o u p E20o, at one m i n u t e af te r in jec t ion there was

a dec rease in M A P ( P < 0 .001) and the B P c o n t i n u e d to

be d i f fe ren t f rom cont ro l af ter t h iopen tone , laryn-

goscopy and unti l three m i nu t e s af ter in tuba t ion ( P <

0 .001) (Tab le II).

A n a l y s e s o f the sys to l ic and d ias to l ic ar ter ial p ressure

c h a n g e s y ie lded resul ts s imi la r to those for M A P

(Tables I l l and IV).

TABLE V Heart rate (bpm) in the three groups: placebo (Group P), esmolol 100 mg (Group E~00) and esmolol 200 mg (Group E2oo)

Group P Group Eto o Group E2o o Time n= 15 n = 15 n = 1 5

Basal 89.0 • 1.9 89.5 • 2.9 93.1 • 2.8 PI 89.7 • 1.7 79.0 • 2.7"t 81.5 • 2.2"1 0 98.7 • 2.7* 86.3 • 2.5t 82.0 • 2.0*t 1 108.2• 86.8 • 2.2t 83.6 • 2.2"t 3 107.1 • 86.4• 83.8 • 2.4"1- 5 102.1 • 1.7" 86.8 • 2.3t 84.9 • 2.4"I 7 cJ8.4 • 1.7" 88.1 • 86.5 • 2.3"t

10 93.2• 1.5, 88.8• 87. •

Note : all values represent mean (bprn) • SEM. Time PI denotes one minute after pre-treatment (with esmolol or saline). *Difference from respective basal value P < 0.05 after Bonferroni correction. tDifference from respective Group P value P < 0.05.

The ef fec t o f e smolo l on hear t rate in the three g roups

is s h o w n in T a b l e V. In the cont ro l g roup , hear t rate

inc reased a b o v e the basal rate f rom the t ime o f laryn-

goscopy and in tuba t ion until the last r ead ing taken af te r

ten minu t e s ( P < 0.001) . In G r o u p E~00 hear t rate

dec reased be low the basal rate one m i n u t e af te r e smolo l

admin i s t r a t i on (P < 0 .001) and, f rom in tuba t ion to the

end o f the s tudy, was c o m p a r a b l e to the basal rate (P >

0.05). In G r o u p Ez00, howeve r , the dec reased rate con-

t inued for up to seven minu te s a f te r i n tuba t ion (P <

0.001) . T h e r e were no d i f f e rences b e t w e e n G r o u p Et0o

and E200 but the con t ro l g roup d i f fe red f rom t h e m bo th

at all t imes excep t for the basal and the 10 rain

pos t - in tuba t ion rates.

No s ide-ef fec ts a t t r ibu tab le to e smolo l ( E C G changes ,

Sharma et al.: ESMOLOL AND HYPERTENSION 781

bronchospasm, hypotension) were observed during the study.

Discussion The results of the present study demonstrate that intravenous esmolol in doses of either 100 mg or 200 mg bolus is effective in attenuating both hypertensive and tachycardia responses to laryngoscopy and tracheal intubation in treated hypertensive patients. This is in agree- ment with earlier studies ~7-n9 that were carried out in normotensive patients.

Complications of the pressor response that follows laryngoscopy include myocardial ischaemia, 2.2~ cardiac failure, 2~ intracranial haemorrhage 21 and increase in intracranial pressure. 22 Studies of hypertensive patients have shown that the pressor response to laryngoscopy is exaggerated in these patients and that it is associated with a marked increase in the noradrenaline concentra- tion in the blood. 4 Surgical patients with hypertension have also been shown to carry an increased risk of perioperative complications. Prys-Roberts et al.n2 found that the tachycardia and pressor response may be partly obtunded by the use of beta-adrenergic antagonists. Magnusson et al. 23 used intravenous metoprolol to pre- vent these reflex cardiovascular responses but that it had long lasting effects that may not be desirable. Esmolol, a short acting beta-adrenergic antagonist has been found to be more suitable for this purpose.

Several pharamacological agents have been used to blunt the haemodynamic responses to laryngoscopy and intubation in normotensive patients. These include topical and systemic lidocaine, 5,6 fentanyl and alfentanyl, 7 buprenorphine, x topical and intranasal nitroglycerine, 1~ metoprolol In.E3 and verapamil. L~ All these studies show that the hypertensive response can be attenuated partially but the associated tachycardia often can not be effectively controlled.

The optimal dose of esmolol to obtund these haemodynamic responses to tracheal intubation has been a subject of discussion. Some previous studies reported that only higher doses of esmolo125'26 obtunded the response effectively although others disagreed. 18.~9 Indeed some authors have found esmolol 100 mg to be as effective as 200 mg; tS.t9 but with fewer side effects. 27 In our study esmolol 100 mg was effective in blunting the haemodynamic response both hypertension and tachycardia. Esmolol 200 mg, on the other hand, caused a sustained decrease in arterial pressure and heart rate. This may be undesirable and potentially hazardous in hypertensive patients. 2

In conclusion, we suggest that the use of esmolol in a dose of 100 mg is a safe and convenient method for attenuating the haemodynamic response to laryngo-

scopy and tracheal intubation in treated hypertensive patients.

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Esmolol blunts the haemodynamic responses to tracheal intubation in treated hypertensive patients

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