A d a anaesth. scand. 1979, 23, 51-56

Restlessness and Shivering after Naloxone Reversal of Fentanyl-supplemented Anaesthesia T. TAMMISTO and I. TICERSTEDT Department of Anaesthesia, Helsinki University Central Hospital, Helsinki, Finland

T o study the significance of normalization of ventilatory or thermal homeostasis during naloxone reversal, 95 patients were given naloxone after thiopental-N2002-relaxant anaesthesia supplemented with fentanyl (6 pg/kg/h). If naloxone 0.16 mg was given to combat postoperative apnoea during hypercapnia (end tidal carbon dioxide concentration (ETco,) 8%), minute ventilation and respiratory rate were significantly higher during the first minutes as compared to the normocapnic patients. Shivering occurred in 44% in the hypercapnic group, as compared to about 30% if naloxone was given during normocapnia (ETCO25%). Postoperative pain and restlessness were significantly increased in the hypercapnic group. During normocapnia, untoward reactions were less frequent (40%) if naloxone was given in smaller increments (0.08+0.08 mg) rather than in one dose (0.16 mg) (72%). This was mainly due to nausea (8% compared to 32%). The incidence and severity of shivering showed a positive correlation to the duration of anaesthesia (r=0.42) and to the total amount of fentanyl (r=0.32), but not to the actual postoperative oesophageal temperature (r = - 0.13). The results indicate that though untoward reactions after naloxone reversal are aggravated by naloxone-induced normalization of deranged homeostatic mechanisms, their aetiology probably should be sought in an acute abstinence syndrome. Received 16 M a y , accepted for Publication 21 June 1978

Naloxone, as a pure narcotic antagonist, is devoid of agonistic properties in clinical dosage (JASINSKI et al. 1967, FOLDES et al. 1969, EVANS et al. 1974). Consequently it is the drug ofchoice in the treatment of narcotic overdosage (FOLDES et al. 1969). However, despite its pure antagonistic nature, untoward effects (e.g. restlessness, shivering, antanalgesia, nausea and vomiting) are often seen during naloxone reversal. Though these have been interpreted as symptoms of acute abstinence (LONGNECKER et al. 1973), it is conceivable that the sudden changes in the homeostatic mechanisms induced by naloxone might affect their incidence and severity (MARTIN1967, HUSEet al. 1974). Thus an abrupt increase in the sensitivity to carbon dioxide of the respiratory centre

would produce symptoms of hypercapnia if naloxone is given to counteract the respiratory depression caused by narcotics. To determine the significance of these mechanisms in the occurrence and severity of the untoward effects during naloxone reversal, we gave single and repeated doses of naloxone during normocapnia and hypercapnia after intraoperative fentanyl administration. Since in the course of the study it seemed as if recovery of thermoregulation might also play a role in the severity of the untoward symptoms, attention was paid to body temperature in another series of patients.

MATERIAL AND METHODS The original study comprised 75 patients in good or

52

T. TAMMISTO AND I. TIGERSTEDT

fair general condition (ASA I or II), who were scheduled for various elective surgical procedures. Anaesthesia After premedication with pethidine 1 mg/kg, promethazine 25-50 mg and atropine 0.1 mg/lO kg, anaesthesia was induced with thiopental (3-5 mg/kg). The patients were intuhated after the administration of 1.5 mg/kg of suxamethonium, preceded by 0.05 mg/kg of d-tubo-curarine. Anaesthesia was maintained with a nitrous oxide-oxygen mixture (70”/,/30%) using IPPVin a nonrebreathingsystem (with unwarmed gases). d T C was given for muscle relaxation and the need for the drug was determined using a peripheral nerve stimulator. Anaesthesia was supplemented with fcntanyl 0.1 mg every 15 min. If the patient still reacted duringsurgery, additional doses offentanyl were given. After surgery, muscle relaxation was reversed with 2 mg of neostigmine and 1 mg of atropine, and the effect was checked with the neurostimulator. ‘Thereafter patients were randomly divided into the following three treatment groups: IngroupN8 (25 patients), the end-tidal C 0 2 (ETco,) was allowed to rise to 8% before 0.16 mg naloxone was given i.v. and the nitrous oxide supply was turned off.

Iu group (25 patients), the end-tidal C 0 2 was maintained a t 5%, 0.16 mg naloxone was given i.v. and the nitrous oxide supply was then turned off.

In group N52 (25 patients), the end-tidal COz was also maintained at 5%, but only 0.08 mg naloxone was given i.v. and the nitrous oxide supply was then turned off. Naloxone 0.08 mg was repeated 7 min after the start of spontaneous respiration when the initial respiratory measurements had been performed. After the start of spontaneous respiration, the pat-

ients were extubated and thc respiratory minute volume and rate were recorded at 1, 3 and 6 min. Blood pressure and heart rate were measured at the same intervals. After these measurements, the patients were transferred to the recovery room where the respiratory rate, blood pressure and pulse rate were measured immediately on arrival, and after 15, 30 and 60 min. Any untoward effects were carefully noted and patients were asked about their subjective sensations. Pain was scored from 0 (no pain) to 3 (severe pain), and shiveringas follows: 0 = no shivering; 1 = hardly visible; 2 = slight; 3 = moderate; and 4 = severe. Oxycodone was given for pain relief when needed, but the pain score for the rest of the observation period was considered to be that found prior to administration of the analgesic. During the study, we got the impression that shivering precipitated by naloxone was more marked after long anaesthesias with potentially greater heat loss. Oesophageal temperature was therefore recorded in 20 additional patients who were otherwise studied in a similar way following abdominal surgery lasting at least 3 h, and to whom 0.16 mg naloxone was administered under normocapnia (ETco, 5%). Oesophageal temperatures were recorded with a n Ellah telethermometer. I n half of the patients, attempts were made to minimize the peroperative heat loss with a nearly closed-circuit breathing system, warmed infusions and transfusions, and by wrapping the patient in a ‘space blanket’ (group N5,). The other half of the patients were anaesthrtixed in the usual way and only the transfusions were warmed (group N5.,). Statistics One analysis of variance or Student’s t-test (whcnevcr appropriate) was used to compare the means of

Table 1 Physical characteristics of the patimts in the different treatment groups. Mean (+s.e. mean) or (range).

N5 I

N ~ z

N8

N5w

N5”,

Sex: male female

14 11

10 15

9 16

6 4

Age (years)

52 (20-72)

46 (28-68)

45 (17-67)

47 ( 18-64)

50 (29-74)

Weight (kg)

73 (52-93)

73 (53-102)

69 (40-100)

72 (62-84)

63 (55-80)

170 (155-189)

169 (1 53 -195)

I69 ( 152-1 89)

171 (147-183)

169 (1 52-1 85)

Height (cm) Preoperative oesophageal temperature ( “ C )

6 4

36.92 & 0.09 36.91 5 0.15

53

RESTLESSNESS AND SHIVERING AFTER NALOXONE

Tablc 2 Distribution of surgical procedures, duration of anaesthesia and total dose of intraoperative fentanyl in the different treatment groups.

N5 I

Treatment groups

N5*

N5

N8

N5", L

Type of surgery: abdominal urologiral superficial Duration of anaesthrsia (min) (range) Dose of fentanyl (mgk s.e.mean) ( K / k / h )( k s.e.mean)

10 4 11

10 -

10

18

10 2 13

102 (40-290)

109 (40-240)

108 (25-270)

245 (180-240)

234 (180435)

0.71+0.07

0.75+0.07

0.71k0.08

1.47-10.11

1.47+0.19

6.020.3

6.0k0.3

6.2k0.4

6.1k0.5

5.1k0.3

7 -

parametric data. The X2-test was used for comparison of non-parametric data.

RESULTS Table 1 shows the physical characteristics of the patients in the different treatment groups. Table 2 shows the type of surgery as well as the duration of anaesthesia and the dosage of fentanyl given in the different treatment groups. Though there seems to be a preponderance of superficial surgery in group N5, (0.08 mg of naloxone twice), the mean durations of anaesthesia and the total amounts of fentanyl given in groups N8, N5, and N5, are quite comparable. The two

-

groups with long-lasting abdominal operations are also comparable in this respect. Figure 1 shows the postnaloxone behaviour of respiration during the initial recovery period (0-6 min) in groups N8, N5, and N5,. The respiratory rate was higher when naloxone was given during hypercapnia (N8) than when it was given during normocapnia (N5, and N5,) ( P < O . O l ) . Also, the respiratory minute volume seemed to be higher in group N8, but here the statistical significance could be ascertained only between groups N8 and N5, at the first minute ( P < 0.01). The changes in blood pressure and heart

N.5,N52---

NH ......

0

'

3

6

MIN POSTNALOXONE

0

1

3 6 MIN POSTNALOXONE

Fig. 1. Respiratory minute volume (0, l/min) and rate (brcatlis/min) during the first 6 min after the start of sponN52, N8) (+s.e.mean) mneous respiration in the differcnt naloxone groups (NEI~,

54

I

T. TAMMISTO AND I. TIGERSTEDT MEAN SHIVERING INTENSITY

N5,--

.. Fig. 2. Mean shivering interisity score (Fs.e.mean) during

01

6

3

MIN POSTNALOXONE

0

15

recovery from anaesthesia in the different naloxone groups 0‘51, N52, N8)

I 60 MIN

- 1

0

30

RECOVERY ROOM PERIOD

rate during the first 6 min were clinically insignificant (