Summary of abstracts

Calcium channel blockers (CCBs) are controversial drugs at best, especially short-acting CCBs used in the context of ischaemic heart disease. Here we look at a completely different aspect of their use - for protection against the ex tubation response. Is this use a good idea? You may also wish to briefly browse our editorial comment

In this study, Yuji and his colleagues use near-infrared spectroscopy (NIRS) to examine the cerebral response to tracheal extubation, in the presence or absence of calcium channel blockers (CCBs).

Although this article is in the section on 'Neurosurgical Anaesthesia', the cases used were all ASA 1 or 2, scheduled for elective gynaecological surgery. Study numbers were not large, with fifteen patients in each of the three groups (controls, nicardipine 0.02 mg/kg, diltiazem 0.2 mg/kg). Group allocation was random; consent was obtained. Nishina's (rather arbitrary) five-point scale was used to rate quality of tracheal extubation - a Kruskal-Wallis test was used to compare scores. Heart rate, blood pressure, and NIRS-derived variables (Hb, HbO ₂ ) were compared within groups using one-way ANOVA, and among groups using repeated measures ANOVA with Student-Newman-Keuls post hoc {Ed: See our previous discussion!}

Intriguingly, the authors provide a graph, and measures of significance, but no numbers when they come to analyse their blood pressure results. In the controls the mean blood pressure (from the graph) appears to increase from a baseline of ~ 95 mmHg to about 110 mmHg, although we are assured "a significant change over time was not seen in each group".

The bottom line of their analysis is that the calcium channel blockers appear to:

1. raise heart rate;
2. attenuate blood pressure response;
3. raise cerebral HbO ₂ even more than in controls, suggesting increased cerebral blood flow.

The authors then speculate extensively, based on the work of Lanier (Anesethesiology 1994 80 392-401) who showed that cerebral oxygen consumption not only increases in response to muscular activity, but may even increase in excess of cerebral demand!! More important than this speculation is their assertion that CCBs increase cerebral blood flow despite 'protecting' against rises in blood pressure during extubation - a worry if were to use these agents to 'blunt the extubation response' in patients undergoing neurosurgery!

Article 1: The effect of calcium channel blockers on cerebral oxygenation during tracheal extubation

Source: Anesthesia & Analgesia 2000 91(2) 347-52

Article type: Clinical study

Author: Yuji M, et al.

Mikawa and colleagues compared intravenous verapamil (0.1mg/kg) and lignocaine (1mg/kg), alone or in combination, with a control group. With a fair sample size (four groups of 25) of patients similar to Yuji's, they found attenuation of the blood pressure response, which was most profound with the combination of the two agents. They appear to use a two-way ANOVA with a post-hoc Bonferroni, incidentally reporting all their results ±SEM to make them look crisp and clear!

The idea of whacking a heady combination of verapamil and lignocaine into a critically poised neurosurgery patient seems far from appealing, even if we were to disregard Yuji's subsequent report! Their conclusion..

 In conclusion, we have shown that a combination of
verapamil 0.1mg/kg and lidocaine 1mg/kg injected
IV two minutes before extubation is a simple, effec-
tive, and practical prophylactic method for suppress-
ing the hypertensive and tachycardic responses to tra-
cheal extubation, and this beneficial effect is superior
to that of each drug alone.

.. nowhere states that this is an extrapolation from fit ASA I patients undergoing elective gynaecologic surgery. He who reads just the conclusion, beware!

The same authors have published similar articles one and two years previously. The 1995 study looked at the response to diltiazem, the one performed in 1996 compared verapamil and diltiazem. The studies are of a similar quality to those already discussed.

Article 2: Attenuation of cardiovascular responses to tracheal extubation: comparison of verapamil, lidocaine and verapamil-lidocaine combination

Source: Anesthesia & Analgesia 1997 85(5) 1005-10

Article type: Clinical study

Author: Mikawa K, et al.

Article 3: Attenuation of cardiovascular responses to tracheal extubation : verapamil versus diltiazem

Source: Anesthesia & Analgesia 1996 82(6) 1205-10

Article type: Clinical study

Author: Mikawa K, et al.

Article 4: Attenuation of cardiovascular responses to tracheal extubation with diltiazem

Source: Anesthesia & Analgesia 1995 80(6) 1217-22

Article type: Clinical study

Author: Nishina K, et al.

Editorial pointers

Japanese researchers seem to have cornered the market when it comes to producing papers on ameliorating the extubation response. In addition to the above, we find Fujii et al reporting on the combination of diltiazem and lignocaine in ASA II hypertensive patients (Can J Anaesth 1999 Oct;46(10):952-6). Nishina and colleagues used IV prostaglandin E1 in two papers (Can J Anaesth 1997 Nov;44(11):1211-4; Can J Anaesth 1996 Jul;43(7):678-83). And so on. Is all this fuss justified? If we go to Pubmed and do a quick, rough search along the lines of: in tubation[ti] AND (haemodynamic[ti] OR hemodynamic[ti] OR cardiovascular[ti]) then we'll get about 180 articles - if we replace the word intubation by ex tubation, the number plummets to thirty! Paulissian and colleagues (Anesth Analg 1991 Jul;73(1):10-5) report that haemodynamic responses on extubation of patients after coronary artery bypass graft were 'modest' and not modified by intravenous lignocaine 1mg/kg IV. Conti and Smith disagree, (Br J Anaesth 1998 Jun;80(6):834-6) recommending ongoing sedation during tube removal after cardiac surgery! An interesting option not mentioned by the Japanese researchers is the use of topical lignocaine instilled into the cuff of the endotracheal tube. In two recent articles, one from Altintas et al (Eur J Anaesthesiol 2000 Jul;17(7):436-42) and another by Fagan and colleagues (Anesth Analg 2000 Jul;91(1):201-5), 10% or 4% lignocaine respectively were instilled, dramatically lowering the incidence of 'bucking' on extubation (from 70% (!) down to 20% in the first study), with less post-extubation cough. Huang and colleagues (Acta Anaesthesiol Sin 1998 Jun;36(2):81-6) reported similar findings two years previously (They warmed and alkalinised their 4% lignocaine). Navarro and Baughman from Chicago showed that even at 24 hours, the incidence of sore throat was substantially less if patients had lignocaine in their cuffs (pre-filled 90 minutes prior to intubation, J Clin Anesth 1997 Aug;9(5):394-7). What are our options? There seem to be several including: Doing nothing to blunt the extubation response; topical lignocaine; Intravenous lignocaine; IV esmolol (J Clin Anesth 1992 Nov-Dec;4(6):444-7; Anesth Analg 1990 Dec;71(6):675-8), or possibly other beta blockers; A short-acting opiate like remifentanil (Br J Anaesth 1999 Oct;83(4):654-6); calcium channel blockers. Of these options, in the absence of evidence to the contrary, the first might conceivably be the best in most patients. In those at high risk of complications of a vigorous cardiovascular response to extubation, (patients following neurosurgery or with underlying ischaemic heart disease), it seems reasonable to employ a short-acting beta blocker like esmolol, or possibly lignocaine. What is particularly disturbing about the papers that focus on the use of calcium channel blockers is that not only do the authors imply that their results can be extrapolated from well to sick patients, but they do not report haemodynamic variables for the hours following administration of often fairly long-acting agents such as verapamil. Yorukoglu et al reported profound hypotension and bradycardia in response to smaller doses of verapamil used to control the haemodynamic response to extubation (Eur J Anaesthesiol 1999 Jul;16(7):462-7). Will the first paper we reviewed stop the cloying ritual publication of small insignificant studies on calcium channel blockers used in the extubation of well patients? We can only hope! Ed

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Date of First Publication : 2000-06-25

Date of Last Update : 2006/10/23

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