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COMPARISON OF NEUROMUSCULAR BLOCK IN THE DIAPHRAGM AND HAND AFTER ADMINISTRATION OF TUBOCURARINE, PANCURONIUM AND ALCURONIUM
British Journal of Anaesthesia 1990; 64: 294-299
COMPARISON OF NEUROMUSCULAR BLOCK IN THE DIAPHRAGM AND HAND AFTER ADMINISTRATION OF TUBOCURARINE, PANCURONIUM AND ALCURONIUM M. C. DERRINGTON AND N. HINDOCHA
four of each muscle). The duration of paralysis in the diaphragm was less than 5 min in five patients who received tubocurarine and in one who received alcuronium; this corresponded to a period of paralysis in the adductor pollicis muscle of more than 25 min in each case. KEY WORDS Monitoring: neuromuscular function. Neuromuscular relaxants: alcuronium, pancuronium, tubocurarine.
We have reported previously [1] the time course of neuromuscular block in the diaphragm and the adductor pollicis muscle of healthy patients after administration of clinical doses of atracurium and vecuronium. Both the onset of paralysis and the reappearance of twitch occurred in the diaphragm before the adductor pollicis muscle. The method used was described and validated in an accompanying paper [2]. Evoked tests of neuromuscular block are most
PATIENTS AND METHODS
The study was approved by the local Ethics Committee and each subject gave full informed consent. We studied 30 patients, ASA I or II, undergoing surgery for varicose veins. Patients with pacemakers and those who were obese were excluded from the study. Each patient was allocated randomly to receive tubocurarine 0.40.5 mg kg"1 (group 1, n = 10), pancuronium 0.070.08 mg kg"1 (group 2, n = 10) or alcuronium 0.2-0.3 mg kg"1 (group 3, n = 10). The anaesthetic technique was standardized: induction with thiopentone and tracheal intubation after administration of suxamethonium 1-1.5 mg kg"1; the patients breathed halothane M. CLAM
DERRINGTON,
M.B.,
CH.B.,
F.F.A.R.C.S.;
NAINA
HINDOCHA, H.N.C. ; University Department of Anaesthesia, Leicester Royal Infirmary, Leicester LEI 5WW. Accepted for Publication: August 18, 1989.
Downloaded from http://bja.oxfordjournals.org/ at New York University on June 3, 2015
appropriate for use during and after surgery, as the quality of voluntary co-operation may be variable. It is important that the same nerve The onset and offset of neuromuscular block stimulating techniques are used if different musin the diaphragm and in the adductor cles are compared because stimulation with needle pollicis muscle were recorded using unilateral electrodes reveals a magnitude of block different supramaximal stimulation of phrenic and ulnar from that obtained by stimulation with transnerves. Thirty patients were allocated randomly cutaneous electrodes [3]. In addition, the same to receive tubocurarine 0.4-0.5 mg kg'', index of muscle response should be compared [4]. pancuronium 0.07-0.08 mg kg-' or alcuronium No data are available comparing the effects of 0.2-0.3 mg kg-'. In all cases the onset of neuroclinical doses of the longer acting neuromuscular muscular block occurred in the diaphragm before blocking drugs on the diaphragm and the adductor adductor pollicis, and spontaneous recovery was pollicis muscles using the same mode of stimuevident first in the diaphragm. There was a lation and recording a similar index of muscle correlation between the time of spontaneous response in anaesthetized patients. The present reappearance of twitch in the diaphragm and in study was undertaken to compare the onset and the adductor pollicis only in the patients who recovery of neuromuscular block in the adductor received pancuronium (r = 0.97, P < 0.05 for pollicis and the diaphragm after administration of reappearance of the first twitch of the train-of tubocurarine, pancuronium and alcuronium. SUMMARY
NEUROMUSCULAR BLOCK OF DIAPHRAGM AND HAND
295
TABLE I. Details of patients in the study: age, sex, weight, premedication, intraoperatnie opioid, neuromuscular blocking (NMB) drug given and dose, height of control diaphragm twitch (Pdi) and stde of the phrenic stimulation. D = diazepam; F=fentanyl; H^hyoscine; M = morphine; P = papaveretum ; T = temazepam Age
(yr)
Sex
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
44 41 54 54 44 45 31 37 40 24 56 56 60 43 35 40 17 57 48 35 23 36 59 42 40 58 56 46 46 45
M M M F M F F M M F F F F F F M F M F F M F F F F F M M F M
Weight Premed. (kg) 60 90 70 50 70 65 50 73 127 60 66 60 66 65 50 95 50 85 73 55 102 80 70 80 62 42 92 78 60 89
Pdi
Opioid
P+H T D T — T D P P T T T T
P+H T P T P — D D D D T T T
D D P D
P F F P F M — — M P F F — P — P —
F M P F M P P F M M — P
and 66% nitrous oxide in oxygen, and opioids were given as required. The drugs used for premedication and analgesia are shown in table I. Evoked twitch in the diaphragm was recorded using the method adapted and validated for use during anaesthesia and surgery by Derrington and Hindocha [2]. In summary, the pressure generated by the diaphragm (transdiaphragmatic pressure (Pdi)) was measured after unilateral phrenic nerve stimulation. Oesophageal and gastric balloons connected to identical pressure transducers (Elcomatic 751 A) were used to measure the respective pressures on each side of the diaphragm and an abdominal strain gauge was used to monitor diaphragm configuration. The phrenic nerve was stimulated transcutaneously with a hand-held stimulating electrode. The Myograph 2000 (Biometer) [5] was used to evoke and record adductor pollicis twitch. Gastric
NMB
(cm H,O)
12.4 Tubocurarine 30 mg Tubocurarine 40 rag 10.0 Tubocurarine 35 mg 10.0 Tubocurarine 25 mg 12.5 Tubocurarine 35 mg 12.5 Tubocurarine 30 mg 11.8 Tubocurarine 25 mg 12.6 Tubocurarine 35 mg 16.1 Tubocurarine 50 mg 12.2 Tubocurarine 25 mg 15.3 Pancuronium 5.5 mg 11.6 9.6 Pancuronium 5.0 rag Pancuronium 5.0 mg 11.0 Pancuronium 5.0 mg 11.9 9.4 Pancuronium 4.0 mg 9.6 Pancuronium 7.0 mg Pancuronium 4.0 mg 10.0 Pancuronium 6.0 mg 10.5 Pancuronium 6.0 mg 12.7 9.2 Pancuronium 4.5 mg Alcuronium 25.0 mg 10.0 Alcuronium 15.0 mg 12.2 9.5 Alcuronium 15.0 mg 9.2 Alcuronium 15.0 mg Alcuronium 15.0 mg 16.8 Alcuronium 12.5 mg 11.8 Alcuronium 22.5 mg 12.8 Alcuronium 18.75 mg 10.0 Alcuronium 12.5 rag . 12.1 Alcuronium 17.5 mg 10.0
Side of stim. L L L R L L L L L L R L L L L L L L L L L L L L L L L L L L
pressure, oesophageal pressure, transdiaphragmatic pressure (by electronic subtraction) and abdominal strain gauge and Myograph outputs were displayed simultaneously on a chart recorder. Supramaximal stimulation of both ulnar and phrenic nerves was performed at a frequency of 1 Hz over several breaths to obtain control Pdi values, which were measured at resting and expiration. The neuromuscular blocker drug was administered and onset of neuromuscular block was taken as the time of disappearance of twitch during supramaximaJ stimulation at a frequency of 1 Hz. Ventilation of the lungs was continued using a Brompton Manley ventilator and a fresh gas flow of 100 ml kg"1 min"1 and the inspired concentration of halothane was reduced. Spontaneous recovery of each muscle was recorded using train-of-four (TOF) stimulation at a frequency of 2 Hz every 10 s. The time of
Downloaded from http://bja.oxfordjournals.org/ at New York University on June 3, 2015
No.
BRITISH JOURNAL OF ANAESTHESIA
296 60 Tubocurarirte
Pancuronium
50 40
i
i
S I30
- I30
hi
o . | 20
P
2 f 20 I' F
10 0
10
10
20
30
40
50
0
60
10
70
20
30
40
50
60
Time toT1 adductor pollicts (min)
Alcuronium
60
Q J 40
~ £30 m -a 20
P
10 0
10
20
30
40
50
60
Time toT1 adductor pollicis (min)
FIG. 1. Relationship between time to spontaneous reappearance of first twitch of the train-of-four (Tl) of adductor poUicis, and time of reappearance of T l diaphragm ( • ) and time of 50 % recovery of T l diaphragm (D M , • ) after administration of tubocurarine 0.4-0.5 mg kg"1, pancuronium 0.07-0.08 mg kg"1 and alcuronium 0.2-0.3 mg kg"1.
spontaneous reappearance of the first twitch of the TOF (Tl) was recorded in all patients for both the diaphragm and adductor pollicis muscles. The time to reappearance of the fourth twitch (T4) of the TOF was recorded for the diaphragm in all patients and in adductor pollicis when operating time allowed. The time at which the first twitch of the TOF of the diaphragm (T1D) reached 50 % of its control height (DJO) was recorded also. All data were collected before antagonism of neuromuscular block and anaesthesia was not prolonged unnecessarily. If surgery was completed before spontaneous recovery of neuromuscular block, the patient was excluded from the study.
RESULTS
Demographic data for patients are shown in table I with the drug and dose administered and control transdiaphragmatic twitch pressures. The results for all patients are displayed in table II. The time to reappearance of T1 D and to 50% recovery of the diaphragm (DM) are recorded for each drug against the time to reappearance of the first twitch of the TOF of adductor pollicis (T1AP) in figure 1. Onset of paralysis in the diaphragm preceded that in adductor pollicis in all patients. Spontaneous reappearance of T1 D occurred in all patients before there was evidence of recovery in
Downloaded from http://bja.oxfordjournals.org/ at New York University on June 3, 2015
Time toT1 adductor pollicis (min)
NEUROMUSCULAR BLOCK OF DIAPHRAGM AND HAND
297
TABLE II. Time of onset and recovery of neuromuscular block (NMB) after tubocurarine 0.4-0.5 mg kg'1 (group 1), pancuronium 0.07-0.8 mg kg'1 (group 2) and alcuronium 0.2-0.3 mg kg'1 (group 3) in diaphragm (D) and in adductor pollicis (AP). For onset of block, time of disappearance of twitch with stimulation at a frequency of 1 Hz is recorded. The times of reappearance of first (Tl) and fourth (T4) twitches of the train-of-four and the time when Tl of the diaphragm reached 50 % of control (D M ) are also shown Time to recovery
Time to onset of NMB (min)
SD
Pancuronium 11 12 13 14 15 16 17 18 19 20 Mean SD
Alcuronium 21 22 23 24 25 26 27 28 29 30 Mean SD
D
AP
T1D
T4 D
D»
T1AP
T4 AP
1.7 0.7 0.9 1.0 0.8 1.0 0.8 0.9 0.9 0.8 0.9 0.3
.9 .2 0.9 .4 .1 .4 .1 .3 .6 .1 .3 0.3
2.4 35.7 24.6 13.7 3.9 7.4 2.4 3.9 19.9 2.9 11.7 11.6
16.4 40.5 40.9 21.8 15.8 19.2 10.8 12.5 33.8 13.9 22.6 11.6
18.9 39.7 43.5 24.1 19.0 23.9 19.9 14.8 32.3 20.2 25.6 9.6
30.3 38.6 57.0 22.4 44.7 30.9 31.4 30.0 35.6 28.0 34.9 9.9
51.3 55.7
0.8 1.0 1.0 0.8 0.9 1.4 1.0 1.1 0.8 1.0 1.0 0.2
0.9 .3 .3 .3 .5 .9 .5 .2 .1 .3 .3 0.3
21.5 19.9 22.2 13.1 9.0 17.3 14.9 30.2 30.2 25.0 20.3 7.0
38.9 30.6 28.8 25.4 20.4 27.4 24.7 48.6 44.8 40.5 33.0 9.5
38.9 36.9 34.4 23.8 22.3 23.9 25.7 50.7 49.7 35.1 34.1 10.4
48.5 46.5 47.4 37.9 33.1 39.8 34.7 55.2 54.3 49.8 44.7 7.9
0.8 0.7 0.8 0.6 0.5 1.3 0.6 0.9 1.0 0.9 0.8 0.2
.6 1 .0 1 .0 0.9 0.9 .8 1 .0 1 .3 1 .4 I .9 1 .3 0.4
8.9 17.4 32.7 18.0 11.8 3.4 15.9 32.1 14.7 12.2 16.7 9.3
22.7 26.5 39.3 31.6 30.3 16.0 30.6 53.3 30.6 29.9 31.1 9.9
20.2 28.4 39.8 30.6 37.2 19.1 30.6 64.4 31.1 22.5 32.4 13.1
45.5 28.2 49.0 55.1 41.4 27.0 47.7 46.7 34.7 27.4 40.3 10.2
adductor pollicis. In five patients in group 1 (tubocurarine) and one in group 3 (alcuronium) this period of diaphragm paralysis was less than 5 min. In these patients, there was no evidence of neuromuscular transmission in adductor pollicis muscle for more than 25 min (range 27-44 min). The mean difference between reappearance of twitch in the two muscles was 23.2 min
36.4 58.1 50.2 63.6 49.6 52.1 8.5
70.3 48.0 56.0 47.2 77.7 59.8 13.6
46.7 59.9 66.7 39.9 82.6 57.9 50.3 57.7 14.1
(95% confidence intervals (95%CI) +0.6 to + 45.8 min) after tubocurarine, 24.4 min (95% CI +20.4 to +28.4 min) after pancuronium and 23.6 min (95% CI +4.4 to +42.8 min) after alcuronium. The mean difference between 50% recovery of T1 D and reappearance of adductor pollicis twitch was 9.2 min (95% CI -7.2 to + 25.7 min) after tubocurarine, 10.6 min (95%
Downloaded from http://bja.oxfordjournals.org/ at New York University on June 3, 2015
Tubocurarine 1 2 3 4 5 6 7 8 9 10 Mean
from NMB (min)
BRITISH JOURNAL OF ANAESTHESIA
298
CI + 2.6 to +18.6min) after pancuronium and 7.9 min (95%CI -17.3 to +33.1 min) after alcuronium. In the pancuronium group there was a linear relationship between the reappearance of (T1AP) and both the time of reappearance of T1 D (correlation coefficient 0.97) and the time of 50 % recovery of T1 D (correlation coefficient 0.94). There was no linear correlation between recovery of neuromuscular transmission in the two muscles after administration of either tubocurarine or alcuronium.
We have investigated the relationship between neuromuscular block in adductor pollicis and in the diaphragm after the administration of clinical doses of the three longer acting neuromuscular blocking drugs in common clinical use. Demonstration of a correlation between durations of action of the drugs in the two muscle groups would allow inference of the state of neuromuscular block as derived from monitoring of the more accessible muscle, the adductor pollicis, to be extrapolated to the diaphragm. In all cases, the onset of neuromuscular block occurred in the diaphragm before adductor pollicis, and spontaneous recovery always occurred first in the diaphragm. Only in the patients who received pancuronium was there any correlation between the time of spontaneous reappearance of twitch in the diaphragm and in the adductor pollicis. In five patients who received tubocurarine and one who received alcuronium, the duration of paralysis in the diaphragm was less than 5 min. In each of these patients a period of more than 25 min elapsed before there was any response to TOF stimulation of the ulnar nerve. We recorded the time to reappearance of twitch in the two muscles, and the time to 50 % recovery of twitch in the diaphragm. It may be argued that other variables such as the time to 10% recovery of twitch height in each muscle or the time between this and 50 % recovery of twitch height would be more appropriate. However, the recovery times were so long for the adductor pollicis muscle that this proved impossible. In addition, the return of the first twitch of the TOF is judged more easily in clinical practice than are the other recovery indices. Other limitations of the technique used here were discussed in detail elsewhere [1, 2]. They
Downloaded from http://bja.oxfordjournals.org/ at New York University on June 3, 2015
DISCUSSION
include the assumption that the Pdi generated by supramaximal phrenic stimulation is equivalent to and thus comparable to adductor pollicis twitch generated by supramaximal ulnar nerve stimulation, the use of halothane for maintaining anaesthesia, and the prior administration of suxamethonium to facilitate tracheal intubation. Our present results suggest that onset of neuromuscular block can always be assumed to have occurred in the diaphragm when it is demonstrable in the adductor pollicis muscle. This has been described before and attributed to the increased blood flow to the diaphragm or to a differing muscle structure allowing better access of the myoneural blocker to the motor endplates in the diaphragm [6]. Because of direct stimulation of the diaphragm by the surgeon and by irritant fluids such as blood, upper abdominal surgery requires a greater degree of diaphragm paralysis. However, monitoring of adductor pollicis twitch may not permit maintenance of paralysis in the diaphragm. Our results suggest that tubocurarine may be the least useful drug in this context; in many patients its action on the diaphragm was very short. Conclusions from studies such as this, with small numbers of patients, must be tentative and may not be applicable to the elderly or to patients with respiratory muscle disorders. However, the monitoring of neuromuscular block in adductor pollicis appears to be useful in determining when tracheal intubation may be performed without the risk of coughing or of muscle movement. The pattern of recovery of diaphragm twitch to approximately 50% of control when adductor pollicis twitch was just discernible was seen in all patients except one given alcuronium. In this patient a further 20 min elapsed before diaphragm twitch height recovered to 50% of control. A similar phenomenon (prolonged recovery phase following the initial reappearance of a muscle response) has been noted in adductor pollicis after administration of alcuronium [7]. The problems of residual neuromuscular block and how best to assess a patient's recovery from muscle relaxant drugs have been the subjects of recent editorial comment [8]. There is debate on which muscles should be assessed to ensure patient safety. Recovery of the diaphragm from the effects of neuromuscular block is important for both adequate coughing and maintenance of alveolar ventilation. Under normal conditions, and in a
NEUROMUSCULAR BLOCK OF DIAPHRAGM AND HAND
REFERENCES 1. Derrington MC, Hindocha N. Comparison of neuromuscular block in the diaphragm and the hand. British Journal of Anaesthesia 1988; 61: 279-285.
2. Derrington MC, Hindocha N. Measurement of evoked diaphragm twitch strength during anaesthesia. Adaptation and evaluation of an existing technique. British Journal of Anaesthesia 1988; 61: 270-278. 3. Stiffel P, Hameroff SR, Britt CD, Cork RC. Variability in the assessment of neuromuscular blockade. Anesthesiology 1980; 52: 436-437. 4. Katz RL. Electromyographic and mechanical effects of suxamethonium and tubocurarine on twitch, tetanic and post-tetanic responses. British Journal of Anaesthesia 1973; 45: 849-859. 5. Viby-Mogensen J, Hansen PH, Jorgensen BC, Ording H, Kann T, Fries B. A new nerve stimulator (Myotest). British Journal of Anaesthesia 1980; 52: 547-550. 6. Chauvin M, Lebrault C, Duvaldestein P. The neuromuscular blocking effect of vecuronium on the human diaphragm. Anesthesia and Analgesia 1987; 66: 117-122. 7. Astley BA, Hughes R, Payne JP. Recovery from neuromuscular blockade following alcuronium administration. British Journal of Anaesthesia 1983; 55: 1164P. 8. Miller RD. How should residual neuromuscular blockade be detected? Anesthesiology 1989; 70: 379-380. 9. Dodgson BG, Knill RL, Clement JL. Curare increases upper airway resistance while reducing ventilatory muscle strength. Canadian Anaesthetists Society Journal 1981; 28: 505-506. 10. Pavlin EG, Holle RH, Schoene RB. Recovery of airway protection compared with ventilation in humans after paralysis with curare. Anesthesiology 1989; 70: 381-385.
Downloaded from http://bja.oxfordjournals.org/ at New York University on June 3, 2015
healthy patient without pre-existing lung disease, a vital capacity manoeuvre can be undertaken with less than 30% of maximum diaphragm strength. However, Dodgson, Knill and Clement [9] have suggested that large increases in upper airway resistance may occur after operation because of residual neuromuscular block; to overcome this would require greater reserves of diaphragm strength. Complete diaphragm recovery may be important therefore, and the ability to maintain adequate tidal volume, vital capacity or arterial carbon dioxide tension may not be the best criteria to ensure patient safety in the absence of constant observation. Pavlin and colleagues [10] have suggested that the ability to raise the head off a pillow for 5 s confirmed the ability to perform manoeuvres which protect the airway from obstruction and aspiration. They demonstrated that the muscles of the upper airway are among the most sensitive to residual neuromuscular block.
299
COMPARISON OF NEUROMUSCULAR BLOCK IN THE DIAPHRAGM AND HAND AFTER ADMINISTRATION OF TUBOCURARINE, PANCURONIUM AND ALCURONIUM M. C. DERRINGTON AND N. HINDOCHA
four of each muscle). The duration of paralysis in the diaphragm was less than 5 min in five patients who received tubocurarine and in one who received alcuronium; this corresponded to a period of paralysis in the adductor pollicis muscle of more than 25 min in each case. KEY WORDS Monitoring: neuromuscular function. Neuromuscular relaxants: alcuronium, pancuronium, tubocurarine.
We have reported previously [1] the time course of neuromuscular block in the diaphragm and the adductor pollicis muscle of healthy patients after administration of clinical doses of atracurium and vecuronium. Both the onset of paralysis and the reappearance of twitch occurred in the diaphragm before the adductor pollicis muscle. The method used was described and validated in an accompanying paper [2]. Evoked tests of neuromuscular block are most
PATIENTS AND METHODS
The study was approved by the local Ethics Committee and each subject gave full informed consent. We studied 30 patients, ASA I or II, undergoing surgery for varicose veins. Patients with pacemakers and those who were obese were excluded from the study. Each patient was allocated randomly to receive tubocurarine 0.40.5 mg kg"1 (group 1, n = 10), pancuronium 0.070.08 mg kg"1 (group 2, n = 10) or alcuronium 0.2-0.3 mg kg"1 (group 3, n = 10). The anaesthetic technique was standardized: induction with thiopentone and tracheal intubation after administration of suxamethonium 1-1.5 mg kg"1; the patients breathed halothane M. CLAM
DERRINGTON,
M.B.,
CH.B.,
F.F.A.R.C.S.;
NAINA
HINDOCHA, H.N.C. ; University Department of Anaesthesia, Leicester Royal Infirmary, Leicester LEI 5WW. Accepted for Publication: August 18, 1989.
Downloaded from http://bja.oxfordjournals.org/ at New York University on June 3, 2015
appropriate for use during and after surgery, as the quality of voluntary co-operation may be variable. It is important that the same nerve The onset and offset of neuromuscular block stimulating techniques are used if different musin the diaphragm and in the adductor cles are compared because stimulation with needle pollicis muscle were recorded using unilateral electrodes reveals a magnitude of block different supramaximal stimulation of phrenic and ulnar from that obtained by stimulation with transnerves. Thirty patients were allocated randomly cutaneous electrodes [3]. In addition, the same to receive tubocurarine 0.4-0.5 mg kg'', index of muscle response should be compared [4]. pancuronium 0.07-0.08 mg kg-' or alcuronium No data are available comparing the effects of 0.2-0.3 mg kg-'. In all cases the onset of neuroclinical doses of the longer acting neuromuscular muscular block occurred in the diaphragm before blocking drugs on the diaphragm and the adductor adductor pollicis, and spontaneous recovery was pollicis muscles using the same mode of stimuevident first in the diaphragm. There was a lation and recording a similar index of muscle correlation between the time of spontaneous response in anaesthetized patients. The present reappearance of twitch in the diaphragm and in study was undertaken to compare the onset and the adductor pollicis only in the patients who recovery of neuromuscular block in the adductor received pancuronium (r = 0.97, P < 0.05 for pollicis and the diaphragm after administration of reappearance of the first twitch of the train-of tubocurarine, pancuronium and alcuronium. SUMMARY
NEUROMUSCULAR BLOCK OF DIAPHRAGM AND HAND
295
TABLE I. Details of patients in the study: age, sex, weight, premedication, intraoperatnie opioid, neuromuscular blocking (NMB) drug given and dose, height of control diaphragm twitch (Pdi) and stde of the phrenic stimulation. D = diazepam; F=fentanyl; H^hyoscine; M = morphine; P = papaveretum ; T = temazepam Age
(yr)
Sex
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
44 41 54 54 44 45 31 37 40 24 56 56 60 43 35 40 17 57 48 35 23 36 59 42 40 58 56 46 46 45
M M M F M F F M M F F F F F F M F M F F M F F F F F M M F M
Weight Premed. (kg) 60 90 70 50 70 65 50 73 127 60 66 60 66 65 50 95 50 85 73 55 102 80 70 80 62 42 92 78 60 89
Pdi
Opioid
P+H T D T — T D P P T T T T
P+H T P T P — D D D D T T T
D D P D
P F F P F M — — M P F F — P — P —
F M P F M P P F M M — P
and 66% nitrous oxide in oxygen, and opioids were given as required. The drugs used for premedication and analgesia are shown in table I. Evoked twitch in the diaphragm was recorded using the method adapted and validated for use during anaesthesia and surgery by Derrington and Hindocha [2]. In summary, the pressure generated by the diaphragm (transdiaphragmatic pressure (Pdi)) was measured after unilateral phrenic nerve stimulation. Oesophageal and gastric balloons connected to identical pressure transducers (Elcomatic 751 A) were used to measure the respective pressures on each side of the diaphragm and an abdominal strain gauge was used to monitor diaphragm configuration. The phrenic nerve was stimulated transcutaneously with a hand-held stimulating electrode. The Myograph 2000 (Biometer) [5] was used to evoke and record adductor pollicis twitch. Gastric
NMB
(cm H,O)
12.4 Tubocurarine 30 mg Tubocurarine 40 rag 10.0 Tubocurarine 35 mg 10.0 Tubocurarine 25 mg 12.5 Tubocurarine 35 mg 12.5 Tubocurarine 30 mg 11.8 Tubocurarine 25 mg 12.6 Tubocurarine 35 mg 16.1 Tubocurarine 50 mg 12.2 Tubocurarine 25 mg 15.3 Pancuronium 5.5 mg 11.6 9.6 Pancuronium 5.0 rag Pancuronium 5.0 mg 11.0 Pancuronium 5.0 mg 11.9 9.4 Pancuronium 4.0 mg 9.6 Pancuronium 7.0 mg Pancuronium 4.0 mg 10.0 Pancuronium 6.0 mg 10.5 Pancuronium 6.0 mg 12.7 9.2 Pancuronium 4.5 mg Alcuronium 25.0 mg 10.0 Alcuronium 15.0 mg 12.2 9.5 Alcuronium 15.0 mg 9.2 Alcuronium 15.0 mg Alcuronium 15.0 mg 16.8 Alcuronium 12.5 mg 11.8 Alcuronium 22.5 mg 12.8 Alcuronium 18.75 mg 10.0 Alcuronium 12.5 rag . 12.1 Alcuronium 17.5 mg 10.0
Side of stim. L L L R L L L L L L R L L L L L L L L L L L L L L L L L L L
pressure, oesophageal pressure, transdiaphragmatic pressure (by electronic subtraction) and abdominal strain gauge and Myograph outputs were displayed simultaneously on a chart recorder. Supramaximal stimulation of both ulnar and phrenic nerves was performed at a frequency of 1 Hz over several breaths to obtain control Pdi values, which were measured at resting and expiration. The neuromuscular blocker drug was administered and onset of neuromuscular block was taken as the time of disappearance of twitch during supramaximaJ stimulation at a frequency of 1 Hz. Ventilation of the lungs was continued using a Brompton Manley ventilator and a fresh gas flow of 100 ml kg"1 min"1 and the inspired concentration of halothane was reduced. Spontaneous recovery of each muscle was recorded using train-of-four (TOF) stimulation at a frequency of 2 Hz every 10 s. The time of
Downloaded from http://bja.oxfordjournals.org/ at New York University on June 3, 2015
No.
BRITISH JOURNAL OF ANAESTHESIA
296 60 Tubocurarirte
Pancuronium
50 40
i
i
S I30
- I30
hi
o . | 20
P
2 f 20 I' F
10 0
10
10
20
30
40
50
0
60
10
70
20
30
40
50
60
Time toT1 adductor pollicts (min)
Alcuronium
60
Q J 40
~ £30 m -a 20
P
10 0
10
20
30
40
50
60
Time toT1 adductor pollicis (min)
FIG. 1. Relationship between time to spontaneous reappearance of first twitch of the train-of-four (Tl) of adductor poUicis, and time of reappearance of T l diaphragm ( • ) and time of 50 % recovery of T l diaphragm (D M , • ) after administration of tubocurarine 0.4-0.5 mg kg"1, pancuronium 0.07-0.08 mg kg"1 and alcuronium 0.2-0.3 mg kg"1.
spontaneous reappearance of the first twitch of the TOF (Tl) was recorded in all patients for both the diaphragm and adductor pollicis muscles. The time to reappearance of the fourth twitch (T4) of the TOF was recorded for the diaphragm in all patients and in adductor pollicis when operating time allowed. The time at which the first twitch of the TOF of the diaphragm (T1D) reached 50 % of its control height (DJO) was recorded also. All data were collected before antagonism of neuromuscular block and anaesthesia was not prolonged unnecessarily. If surgery was completed before spontaneous recovery of neuromuscular block, the patient was excluded from the study.
RESULTS
Demographic data for patients are shown in table I with the drug and dose administered and control transdiaphragmatic twitch pressures. The results for all patients are displayed in table II. The time to reappearance of T1 D and to 50% recovery of the diaphragm (DM) are recorded for each drug against the time to reappearance of the first twitch of the TOF of adductor pollicis (T1AP) in figure 1. Onset of paralysis in the diaphragm preceded that in adductor pollicis in all patients. Spontaneous reappearance of T1 D occurred in all patients before there was evidence of recovery in
Downloaded from http://bja.oxfordjournals.org/ at New York University on June 3, 2015
Time toT1 adductor pollicis (min)
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TABLE II. Time of onset and recovery of neuromuscular block (NMB) after tubocurarine 0.4-0.5 mg kg'1 (group 1), pancuronium 0.07-0.8 mg kg'1 (group 2) and alcuronium 0.2-0.3 mg kg'1 (group 3) in diaphragm (D) and in adductor pollicis (AP). For onset of block, time of disappearance of twitch with stimulation at a frequency of 1 Hz is recorded. The times of reappearance of first (Tl) and fourth (T4) twitches of the train-of-four and the time when Tl of the diaphragm reached 50 % of control (D M ) are also shown Time to recovery
Time to onset of NMB (min)
SD
Pancuronium 11 12 13 14 15 16 17 18 19 20 Mean SD
Alcuronium 21 22 23 24 25 26 27 28 29 30 Mean SD
D
AP
T1D
T4 D
D»
T1AP
T4 AP
1.7 0.7 0.9 1.0 0.8 1.0 0.8 0.9 0.9 0.8 0.9 0.3
.9 .2 0.9 .4 .1 .4 .1 .3 .6 .1 .3 0.3
2.4 35.7 24.6 13.7 3.9 7.4 2.4 3.9 19.9 2.9 11.7 11.6
16.4 40.5 40.9 21.8 15.8 19.2 10.8 12.5 33.8 13.9 22.6 11.6
18.9 39.7 43.5 24.1 19.0 23.9 19.9 14.8 32.3 20.2 25.6 9.6
30.3 38.6 57.0 22.4 44.7 30.9 31.4 30.0 35.6 28.0 34.9 9.9
51.3 55.7
0.8 1.0 1.0 0.8 0.9 1.4 1.0 1.1 0.8 1.0 1.0 0.2
0.9 .3 .3 .3 .5 .9 .5 .2 .1 .3 .3 0.3
21.5 19.9 22.2 13.1 9.0 17.3 14.9 30.2 30.2 25.0 20.3 7.0
38.9 30.6 28.8 25.4 20.4 27.4 24.7 48.6 44.8 40.5 33.0 9.5
38.9 36.9 34.4 23.8 22.3 23.9 25.7 50.7 49.7 35.1 34.1 10.4
48.5 46.5 47.4 37.9 33.1 39.8 34.7 55.2 54.3 49.8 44.7 7.9
0.8 0.7 0.8 0.6 0.5 1.3 0.6 0.9 1.0 0.9 0.8 0.2
.6 1 .0 1 .0 0.9 0.9 .8 1 .0 1 .3 1 .4 I .9 1 .3 0.4
8.9 17.4 32.7 18.0 11.8 3.4 15.9 32.1 14.7 12.2 16.7 9.3
22.7 26.5 39.3 31.6 30.3 16.0 30.6 53.3 30.6 29.9 31.1 9.9
20.2 28.4 39.8 30.6 37.2 19.1 30.6 64.4 31.1 22.5 32.4 13.1
45.5 28.2 49.0 55.1 41.4 27.0 47.7 46.7 34.7 27.4 40.3 10.2
adductor pollicis. In five patients in group 1 (tubocurarine) and one in group 3 (alcuronium) this period of diaphragm paralysis was less than 5 min. In these patients, there was no evidence of neuromuscular transmission in adductor pollicis muscle for more than 25 min (range 27-44 min). The mean difference between reappearance of twitch in the two muscles was 23.2 min
36.4 58.1 50.2 63.6 49.6 52.1 8.5
70.3 48.0 56.0 47.2 77.7 59.8 13.6
46.7 59.9 66.7 39.9 82.6 57.9 50.3 57.7 14.1
(95% confidence intervals (95%CI) +0.6 to + 45.8 min) after tubocurarine, 24.4 min (95% CI +20.4 to +28.4 min) after pancuronium and 23.6 min (95% CI +4.4 to +42.8 min) after alcuronium. The mean difference between 50% recovery of T1 D and reappearance of adductor pollicis twitch was 9.2 min (95% CI -7.2 to + 25.7 min) after tubocurarine, 10.6 min (95%
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Tubocurarine 1 2 3 4 5 6 7 8 9 10 Mean
from NMB (min)
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CI + 2.6 to +18.6min) after pancuronium and 7.9 min (95%CI -17.3 to +33.1 min) after alcuronium. In the pancuronium group there was a linear relationship between the reappearance of (T1AP) and both the time of reappearance of T1 D (correlation coefficient 0.97) and the time of 50 % recovery of T1 D (correlation coefficient 0.94). There was no linear correlation between recovery of neuromuscular transmission in the two muscles after administration of either tubocurarine or alcuronium.
We have investigated the relationship between neuromuscular block in adductor pollicis and in the diaphragm after the administration of clinical doses of the three longer acting neuromuscular blocking drugs in common clinical use. Demonstration of a correlation between durations of action of the drugs in the two muscle groups would allow inference of the state of neuromuscular block as derived from monitoring of the more accessible muscle, the adductor pollicis, to be extrapolated to the diaphragm. In all cases, the onset of neuromuscular block occurred in the diaphragm before adductor pollicis, and spontaneous recovery always occurred first in the diaphragm. Only in the patients who received pancuronium was there any correlation between the time of spontaneous reappearance of twitch in the diaphragm and in the adductor pollicis. In five patients who received tubocurarine and one who received alcuronium, the duration of paralysis in the diaphragm was less than 5 min. In each of these patients a period of more than 25 min elapsed before there was any response to TOF stimulation of the ulnar nerve. We recorded the time to reappearance of twitch in the two muscles, and the time to 50 % recovery of twitch in the diaphragm. It may be argued that other variables such as the time to 10% recovery of twitch height in each muscle or the time between this and 50 % recovery of twitch height would be more appropriate. However, the recovery times were so long for the adductor pollicis muscle that this proved impossible. In addition, the return of the first twitch of the TOF is judged more easily in clinical practice than are the other recovery indices. Other limitations of the technique used here were discussed in detail elsewhere [1, 2]. They
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DISCUSSION
include the assumption that the Pdi generated by supramaximal phrenic stimulation is equivalent to and thus comparable to adductor pollicis twitch generated by supramaximal ulnar nerve stimulation, the use of halothane for maintaining anaesthesia, and the prior administration of suxamethonium to facilitate tracheal intubation. Our present results suggest that onset of neuromuscular block can always be assumed to have occurred in the diaphragm when it is demonstrable in the adductor pollicis muscle. This has been described before and attributed to the increased blood flow to the diaphragm or to a differing muscle structure allowing better access of the myoneural blocker to the motor endplates in the diaphragm [6]. Because of direct stimulation of the diaphragm by the surgeon and by irritant fluids such as blood, upper abdominal surgery requires a greater degree of diaphragm paralysis. However, monitoring of adductor pollicis twitch may not permit maintenance of paralysis in the diaphragm. Our results suggest that tubocurarine may be the least useful drug in this context; in many patients its action on the diaphragm was very short. Conclusions from studies such as this, with small numbers of patients, must be tentative and may not be applicable to the elderly or to patients with respiratory muscle disorders. However, the monitoring of neuromuscular block in adductor pollicis appears to be useful in determining when tracheal intubation may be performed without the risk of coughing or of muscle movement. The pattern of recovery of diaphragm twitch to approximately 50% of control when adductor pollicis twitch was just discernible was seen in all patients except one given alcuronium. In this patient a further 20 min elapsed before diaphragm twitch height recovered to 50% of control. A similar phenomenon (prolonged recovery phase following the initial reappearance of a muscle response) has been noted in adductor pollicis after administration of alcuronium [7]. The problems of residual neuromuscular block and how best to assess a patient's recovery from muscle relaxant drugs have been the subjects of recent editorial comment [8]. There is debate on which muscles should be assessed to ensure patient safety. Recovery of the diaphragm from the effects of neuromuscular block is important for both adequate coughing and maintenance of alveolar ventilation. Under normal conditions, and in a
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REFERENCES 1. Derrington MC, Hindocha N. Comparison of neuromuscular block in the diaphragm and the hand. British Journal of Anaesthesia 1988; 61: 279-285.
2. Derrington MC, Hindocha N. Measurement of evoked diaphragm twitch strength during anaesthesia. Adaptation and evaluation of an existing technique. British Journal of Anaesthesia 1988; 61: 270-278. 3. Stiffel P, Hameroff SR, Britt CD, Cork RC. Variability in the assessment of neuromuscular blockade. Anesthesiology 1980; 52: 436-437. 4. Katz RL. Electromyographic and mechanical effects of suxamethonium and tubocurarine on twitch, tetanic and post-tetanic responses. British Journal of Anaesthesia 1973; 45: 849-859. 5. Viby-Mogensen J, Hansen PH, Jorgensen BC, Ording H, Kann T, Fries B. A new nerve stimulator (Myotest). British Journal of Anaesthesia 1980; 52: 547-550. 6. Chauvin M, Lebrault C, Duvaldestein P. The neuromuscular blocking effect of vecuronium on the human diaphragm. Anesthesia and Analgesia 1987; 66: 117-122. 7. Astley BA, Hughes R, Payne JP. Recovery from neuromuscular blockade following alcuronium administration. British Journal of Anaesthesia 1983; 55: 1164P. 8. Miller RD. How should residual neuromuscular blockade be detected? Anesthesiology 1989; 70: 379-380. 9. Dodgson BG, Knill RL, Clement JL. Curare increases upper airway resistance while reducing ventilatory muscle strength. Canadian Anaesthetists Society Journal 1981; 28: 505-506. 10. Pavlin EG, Holle RH, Schoene RB. Recovery of airway protection compared with ventilation in humans after paralysis with curare. Anesthesiology 1989; 70: 381-385.
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healthy patient without pre-existing lung disease, a vital capacity manoeuvre can be undertaken with less than 30% of maximum diaphragm strength. However, Dodgson, Knill and Clement [9] have suggested that large increases in upper airway resistance may occur after operation because of residual neuromuscular block; to overcome this would require greater reserves of diaphragm strength. Complete diaphragm recovery may be important therefore, and the ability to maintain adequate tidal volume, vital capacity or arterial carbon dioxide tension may not be the best criteria to ensure patient safety in the absence of constant observation. Pavlin and colleagues [10] have suggested that the ability to raise the head off a pillow for 5 s confirmed the ability to perform manoeuvres which protect the airway from obstruction and aspiration. They demonstrated that the muscles of the upper airway are among the most sensitive to residual neuromuscular block.
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