Acta Anaesthesiol Scand 1984: 28: 147-151

Effect of Epidural Morphine on Post-operative Pulmonary Dysfunction F. BONNET, CH. BLERY, M. ZATAN, 0. SIMONET, D. BRACE and J. GA~JDY Department of Anaesthesia (D.A.R. 11), Hopital H. Mondor, Creteil and Department of Anaesthesia, Hopital Rotszhild, Paris, France

The effect of post-operative epidural morphine analgesia on pulmonary function was assessed after abdominal surgery and compared to conventional analgesia. In a control group, ten patients received a parenteral analgesic, non-narcotic drug. In a second group of 11 patients, epidural morphine was injected after the operation and continuous analgesia was prolonged until the 3rd post-operative day by means of repeated injections through an epidural catheter. Analgesia was tested on a visual pain scale. Pulmonary function was evaluated by measurements of blood gases, pulmonary volumes (vital capacity, by spirometry, and functional residual capacity by helium dilution technique) and forced expiratory volume in one second. Measurements were performed on the day before the operation and on the first, third and sixth post-operative days. Pain scoring documented a better analgesia in the epidural group during the post-operative period. By contrast, epidural morphine was unable significantly to improve VC, FEV, and FRC during the post-operative course. The results suggest that pain is not an important factor of decreased post-operative pulmonary function.

Received I8 October 1982, accepted for publicaiion 18 F e b r u q I983

Key words: Analgesia; epidural anaesthesia; opiates; pain; post-operative complications; pulmonary volumes.

:I, G - -

Pulmonary function is greatly impaired following ab- dominal surgery (1, 2, 3). Total lung capacity and its subdivisions are decreased and prolonged hypoxaemia is observed in the post-operative period (1). Decreased lung volumes allow airway closure above functional residual capacity (FRC) and consequently the develop- ment ofregions with a low ventilation/perfusion ratio (3, 4, 5). Pain has been suggested to be an important mechanism implicated in post-operative pulmonary dysfunction and morbidity (6, 7, 8).

The effect of' pain relief on pulmonary condition has been studied using either epidural analgesia with local anaesthetics or administration of parenteral opiates. Both techniques have clinical disadvantages: central respiratory depression has been observed with parenteral opiates; cardiovascular side effects, muscle paralysis and the need for repeated injections in the epidural space with the use of local anesthetics. Recently, epidural opiates have been reported to induce an excellent segmental and selective analgesia of long duration (9, 10). We were interested to evaluate the effects of this analgesic technique on post-operative pulmonary func- tion.

PATIENTS AND METHODS This study was conducted over a period of 8 days on 21 patients undergoing colonic or rectal resection. The operation was performed

through a median incision from the pubis to 15 cm above the umbilicus.

All the patients were given 10 mg i.m. diazepam as premedication. Anaesthesia was induced with thiopentone followed by succinyl- choline, and after orotracheal intubation maintained with 70% nitrous oxide in oxygen, supplemented with droperidol, phenoperidine and pancuronium. Patients were extubated at the end of anaesthesia after reversal of residual neuromuscular blockade when necessary. No patients needed naloxone for reversal of the opiate effect.

The aim of the study was to compare a group ofpatients receivinga potent and continuous analgesia to a control group of patients receiving only analgesia without opiates, on demand. For this purpose, on the day before the operation, patients were allocated randomly to two groups, each receiving one of the two post-operative analgesic techniques. The control group consisted of ten patients receiving an anticholinergic analgesic (baralgine) on demand by i.m. injection. The epidural morphine group consisted of 11 patients. In this group, at the end of the surgical procedure an epidural catheter was inserted at the L2-L3 level. An initial dose of 0.1 mg/kg morphine chlorhydrate, diluted in 5-10 ml ofan isotonic saline solution, was injected. The first injection was performed in the recovery room, as soon as patients complained of pain. Daily injections were given until the third post- operative day. Analgesic level was estimated by sensitivity to noxious cutaneous stimuli. The epidural catheter was withdrawn on the morning of the third post-operative day, after a last injection. Post- operative pain was assessed by patients themselves on a visual linear analogue scale, graded from 0 (no pain) to 20 (the most severe pain imaginable) after adequate and detailed explanation had been given by the same operator (1 1). Each patient scored his pain in the morning, recording his overall pain over the past 24 h. Pain scores were established from the first to the sixth post-operative day. Lung function study

Pulmonary function was studied in every patient on theday before {he

148 F. BONNET ET AI,

operation and on the morning 0 1 the lst, 3rd and 6th post-operative days. All measurements were taken by the same operator who was unaware of the patient's pain scoring. Measurements were performed at the bedside, while patients were breathing room air in a semi- reclining position. FRC was measured using the closed circuit helium dilution technique (12), with a Godart FRC computer. Patients wore a nose clip and breathed from a flanged mouthpiece. The spirometer was lilled with air, oxygen and helium to give an initial helium concentra- tion ranging from 13 to 1576, and an oxygen concentration of about 21 %. The patient was thereafter connected to the spirometer. The initial and final helium concentrations were read using a digital voltmeter. The final helium concentration was determined after a 30 s period of stable voltmeter readings during quiet normal breathing. Inspiratory capacity (IC), expiratory reserve volume (ERV) and forced expiratory volume in 1 s (FEVl) were then measured with the Godart expirograph and corrected for BTPS.

A 2-h interval was observed during the post-operative period between the epidural morphine or parenteral analgesic injections and the lung function measurements. At the same time arterial blood samples were taken lor blood gas analysis while patientswere breathing room air. The alveolar-arterial POP difference (A-aDoz mmHg) was calculated as follows: A-anon=(PB - PH~o) Fioz - (Pacos) - Paon where PB = barometric pressure; PHPO= water vapour pressure; Fion=O.Zl; and R=0.8.

In the two groups, all patients were submitted post-operatively to chest physiotherapy twice a day. A chest x-ray was taken pre- operatively and on the third post-operative day.

Statistical analysis used variance analysis, the modified t-test for intra-group comparisons and the comparisons ofvariance and t-test on unpaired data for intergroup comparisons. The Fisher test or comparison of observed percents and linear regression were used when appropriate. The level of significance used was P<0.05.

RESULTS Clinical status The control group consisted of four men and six women and the epidural morphine group ofeight men and three women. The mean age was 60.6k 14.7 (s.d.) years in the control group and 60.2t-18.1 years in the epidural group. Surgery included six colonic and four rectal operations in the control group and four colonic and seven rectal operations in the epidural morphine group. The duration of surgical procedure was 5 . 6 f 1.0 (s.d.1 h and 5.6f1.4 h, respectively, in the control and the epidural morphine groups.

A nalgesia In the control group, patients received parenteral analgesic until the third post-operative day. The mean dose was2.8+0.4and2.4*0.3 injectionson the first and second days, respectively. In the second group, after epidural morphine injection, the analgesic level ex- tended from S5 to T4-T6. In this group the mean duration of analgesia was 15.4f4.2 h, ranging from 10 to 24 h. Two patients complained of itching. Since an indwelling bladder catheter was inserted, urine reten- tion was never observed. Return of bowel motility

"I PAIN SCORE

7

5 p T E M .

1 2 3 4 5 6

Fig. 1. Evaluation of analgesia obtained with epidural morphine during the post-operative period. C.: control group; E.M.: epidural morphine group. * P<0.05; ** P<O.OI (statistical significance of intergroup comparisons of mean values).

occurred between the third day and the fifth day in the two groups. Pain scoring documented a clearly beneficial eflect of epidural morphine compared to the control group (Fig. 1). After the epidural catheter was with- drawn, pain increased slightly and insignificantly in the second group. Pain score remained less in this group than in the first group on days 5 and 6, but the difference was not significant.

Pulmonary function Post-operatively, in the control group, there was a reduction in lung volumes (Table 1). This decrease in VC and FRC reached a maximum on the first post- operative day. The reduction in FRC reached 25 % ofthe pre-operative value (Fig. 2) and was associated with a greater reduction in FEVl, IC, ERV and VC (Table 1). On the 6th post-operative day, these values had not reached control values. By contrast, the FEVl/VC ratio remained constant. In the epidural morphine group, the decrease in lung volumes and FEVl was less important although the difference between the two groups was never significant (Fig. 2). Furthermore, on the sixth post-operative day FRC was restored to its pre-operative value. Arterial blood gas showed post-operative hypoxaemia and an increase in A-ano7 which was identical in the two groups (Table 2). At the same time, the Pacop remained constant in the two groups. Post- operative hypoxaemia and increase in A-an02 correlated with changes in FRC on the first and third post- operative days (r=0.6 P<O.Ol; r z 0 . 6 P<O.Ol).

On the third post-operative day, chest x-ray docu- mented subsegmental atelectasis in four cases in the

EPIDURAL MORPHINE AKD POS?'-OPERATIVE PULMON.4RY FUNCTIOK 149

Table 1

Spirometry before and after surgery.

FRC

vc

ERV

IC

FEVl

FEVl/VC

TV

R R

v

1 s t day 3rd day Pre-op. post-op. post-op.

C 3 118 f 1221 2332f 765"' 2424f711" M 2789t1083 2212f 1236*"* 2298 1 1289"""

C 3277 t 788 2002f 870""" 2195f 641""" M 3761f 927 2502 t 1193*"* 2592 f 1087'""

C 839f 321 4 0 5 i 240""" 524f 177"" M 810f 318 562f 318"" 6051 304'"

C 17351 512 9 8 4 1 590""" 1111f 358*"' M 2310f 914 14761 956""" 1456f 934"""

C 2236 t 699 M 24801 829

C M

C M

6 8 1 10 6 5 f 12

732f 228 707f 252

12755 525** 1547f 484* 18141 1002" 1643f 779""

66+ 13 6 4 f 13

6 9 f 10 61+ 10

5 8 3 1 197" 607f 128" 5 7 3 1 151'" 558f 185"

c 15.5f 1.8 17 .0f 4.4 15 .7f 3.7 M 16.4f 4.5 19.0f 4.4 19 .41 5.1

C 10817f3774 9380 f2845 9368 f2404 M 10671 f2763 9520t1372 101 38 f 1900

6th day post-op.

~

2478f 722 2943f1418

2565f 848 3355f1366

709f 241" 7 1 0 1 475

1301f 558" 1624k 673""

1794+ 444 2221 *I066

6 7 f 7 6 2 1 10

652f 68 6 9 0 1 213

18 1 5.2 17.4+ 4.1

1 1923 f 4023 1185 f3502

meanks.d.; " P<0.05; ** P<O.O2; "** P<O.OOl. P values indicate, in each group, the statistical significance of the differences between pre- and post-operative mean values. FRC: functional residual capacity (ml); VC: vital capacity (ml); ERV: expiratory reserve volume (ml); IC: inspiratory capacity (ml); FEV1: forced expiratory volume in 1 s (ml); TV: tidal volume (mi); RR: respiratory rate (/min); V: minute ventilation (ml); C: control group; M: epidural morphine group.

DISCUSSION The post-operative course of colonic or rectal surgery is well known to be extremely painful. Potent and pro- longed analgesia induced by epidural morphine would be expected to improve the alleged consequences ofpain on pulmonary function. In fact, our results show that post-operative epidural morphine restores pulmonary dysfunction only partly.

epidural group and in two cases in the control group; the difference was not statistically significant.

No significant difference appeared in the two groups in the duration of post-operative stay (control group: 18.5k6.4 days (s.d.), morphine group 19.0k6.8 days).

d

As expected, in the control group, patients docu- mented arterial hypoxaemia and a drastic decrease in lung volumes compared to the pre-operative values. These results were in the same range as previously reported data for abdominal surgery (8, 13). Further- more, pulmonary dysfunction and hypoxaemia persisted until a t least the 6th post-operative day.

In our study, epidural morphine slightly improved the restrictive impairment of lung volumes. Indeed, epidu- ral analgesia was found to improve recovery in VC and FRC. Hypoxaemia was not significantly altered by epidural morphine. An improvement in vital capacity has previously been reported in the post-operative period after epidural analgesia with local anaesthetics

Fig. 2. Changes in FRC and VC following surgery. C.G.: control group; M.G.: epidural morphine group; C.: control pre-operative value=100%. * P<0.05; "* P < O . O l (statistical significance between (14, 15), but the effects O f On FRC are pre- and post-operative values in each group). not as well documented. Wahba et al. noticed an

150 F. BONNET ET A I .

Table 2 Post-operative values of arterial POZ and PCOZ and of a-Aoo?.

Paoe mmHg (kPa)

A-am2 mmHg ( H a )

Pacoz mmHg (Wa)

1st day Pre-op. post-op.

C 80.0f 8.6 (10 .6kl . l ) 71.5*f 8.6 (9 .5*f l . l ) M 81.3110.7 (10.8f1.4) 65.7*f10.9 (8.7'f1.4)

C 26 f 7 (3.5f0.9) 37% f 6 (4.9*f0.8) M 23 f 1 2 (3.1+0.5) 42* f l l (5.6'f1.5)

C 37 f 4 (4.9k0.5) 34.9 * 4.5 (4.6 k0.6) M 37.4* 4.1 (5.010.5) 37.2 f 2.9 (4.9 +0.4)

3rd day post-op.

64.6**10.8 (8.6*f1.4) 66.5'f 9.4 (8.8**1.2)

45* f 1 4 (6.0*f1.9) 42' f10 (5.6**1.3)

34.2 * 1.9 (4.5 10.2) 35.2 f 3.1 (4.7 f 0 . 4 )

6th day post-op.

71.0f17.5 (9.4 f 2 . 3 ) 70.0f10.7 (9.3 f 1 . 4 )

44* f 1 6 (5.9**2.1) 34 f 1 2 (4.5 f 1 . 6 )

33.0+ 1.8 (4.4 f0 .2 ) 35.6f 2.1 (4.7 i0 .3 )

Mean f s.d.; ' P<0.05 (statistical significance ofdifference betweenpre- and post-operativevalues) C: control group; M: epiduralmorphine group.

immediate but slight increase in FRC in patients with pain who benefited from epidural anaesthesia (15). This was not confirmed by Drummond & Littlewood in a 24 h study conducted on patients submitted to lower abdominal surgery (13). In a randomized study, Spence & Logan (14) documented a beneficial effect ofepidural anaesthetics on FRC; the difference was significant compared to parenteral opiate analgesia, but only on the 5th post-operative day. Furthermore, arterial hypox- aemia has been shown to be improved (16, 17) or unchanged (18) after epidural anaesthesia.

Epidural anaesthesia by itself was considered not to change FRC in healthy men (19, 20). In fact, a body- mass index and age-related decrease in FRC has recently been reported to be induced by intercostal blockade with bupivacaine (21). In this respect, epidural morphine seems to have some theoretical advantages compared to local anaesthetics. Firstly, analgesia is selective without any problems of abdominal or inter- costal muscles blockade which could impair the ven- tilatory pattern. Secondly analgesia is stable and of long duration without the need for repeated injections. Only three studies have investigated the ef'fects of epidural morphine in the post-operative period after abdominal surgery (22, 23, 24).

An immediate improvement in FEVl was docu- mented in the recovery room by Bromage et al., after analgesia had been established, and the best result was obtained with epidural morphine (22). After gall bladder surgery, Rawal et al. (23) found a significant improve- ment in the peak expiratory flow following an epidural injection of 4 mg of morphine. 1.m. opiates or epidural bupivacaine resulted in less marked recovery. In these two studies no data were given concerning the corresponding FRC and blood gases. In a more recent study on the post-operative course of cholecystectomy, Rybro et al. reported a better Paop and a less marked A- aDo2 in patients receiving epidural morphine, compared to patients receiving i.m. morphine on demand (24).

However, this was not related to a better analgesia or to a difkrence in lung function parameters. Furthermore, patients in the i.m. morphine groups were 7.5 years older than those in the epidural morphine group and seemed to have a worse pre-operative pulmonary condition. This could impair the interpretation of their post- operative data (25).

In our study, the incomplete improvement of pul- monary dysfunction documented after epidural morphine could be explained in several difyerent ways. Firstly one could argue that complete pain sedation was not obtained in our patients. Nevertheless, the observed level of analgesia was always above the pain location. Furthermore, we used morphine doses higher than those previously reported to be effective in the post-operative course after abdominal surgery (10, 26). Despite these subsequent epidural morphine doses, coughing and deep breathing sometimes remained painful. Neverthe- less, a statistical improvement in pain score was obtained compared to the control group, and the evaluation of pain relief was confirmed by the opinion of the other members of the medical staff (nurses and chest-physio- therapists), who noted that patients in the morphine group felt more comfortable.

Epidural morphine has been documented to depress the ventilatory response to Cop for several hours (27, 28). In our patients no significant ventilatory depression was observed and naloxone was never used to antagonise bradypnoea. At the same time when pulmonary volumes were measured, arterial Pacop was in the same range in the two groups of patients. Consequently, alveolar hypoventilation is not likely to be the mechanism ofpost- operative hypoxaemia in the epidural morphine group.

We found, like others (29), that hypoxaemia and A- aDOz were related to the changes in FRC in the post- operative period, but controversial data have been reported (14). This discrepancy could be explained by the fact that multiple factors are implicated in post- operative hypoxaemia (29). By contrast, no correlation

EPIDURAL MORPHINE AND POST-OPERATIVE PULMONARY FUNCTION 151

was documented between the changes in FRC and the pain scores, leading to the conclusion that pain is not the main mechanism of decreasing FRC. Nevertheless, the slightly better recovery of FRC andVC, observed on the 6th post-operative day in the epidural morphine group, could be explained as the effect of the better compliance to chest physiotherapy. Finally the duration of hospital stay was not modified by epidural morphine analgesia in our study.

In conclusion, our results show that pain relief with epidural morphine dramatically improves the patients' comfort but fails to change their pulmonary condition. It is thus suggested that pain is not the most important mechanism of decrease in FRC and impairment in pulmonary function.

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Address F. Bonnet, M.D. Department of Anaesthesia (D.A.R. 11) Hopital H. Mondor 51 Avenue du Marechal de Lattre de Tassigny 94010 Creteil Cedex, France