In the last decade, spinal anaesthesia became the commonest pain relief method used for Caesarean sections [1]. Thanks to this anaesthesia, a woman in labour is able to participate actively in the delivery; moreover, the method is safer than general anaesthesia, for both the mother and the newborn. During Caesarean section, the peritoneum is strongly pulled causing the visceral pain. With hyperbaric bupivacaine, high sensory blockade reaching Th4-Th6 may be insufficient and additional intraoperative analgesia is required [2]. Higher doses of bupivacaine increasing the level of blockade are likely to enhance hypotension and induce breathing difficulties [2, 3].

In order to limit the adverse effects, local anaesthesia (LA) agents are combined with low doses of opioids. Administered subarachnoidally, they allow to reduce the dose of bupivacaine, improve the quality of intraoperative analgesia and their analgesic effects last in the postoperative period [4, 5].

The subarachnoid administration of opioids is based on the concept of multimodal analgesia acting at various levels of pain conduction. The use of various drugs and methods limits their adverse side effects and increases the analgesic efficacy.
The combination of opioids with LA agents administered subarachnoidally for intra- and postoperative analgesia seems promising. Although they have been used since the 70-ties, the issues regarding the proper opioid choice and dosage are still discussed.

The aim of the study was to assess the effects of subarachnoid opioids on postoperative analgesia and demands for iv opioids administered by the patient-controlled analgesia (PCA) method in the postoperative period.

METHODS

The prospective, randomized, double-blind study was designed, which was approved by the Bioethics Committee, Medical University of Warsaw. The study involved ASA I-II pregnant women scheduled for elective Caesarean sections. The exclusion criteria were: no consent for the study protocol, contraindications for block anaesthesia or any of the protocol agents and surgery due to other than elective indications.

Patients were divided into 2 groups: in the first group, fentanyl was used with the LA agent (group F), in the other one – morphine (group M).

Standard monitoring involved ECG, SpO2, non-invasive measurements of arterial pressure every 2 min. After transfusion of the Ringer’s solution 1000 mL, the parturient was placed in the right lateral decubitus position. Spinal anaesthesia was performed with a 27G needle in the L3-L4 or L4-L5 space and the patient was positioned in the supine position with left-hand inclination (15°). The doses of bupivacaine were adjusted to the height (from 7.5 mg for women <150 cm to 15 mg for those >172 cm of height). The LA agent was supplemented with 25 μg of fentanyl in group F and 100 μg of morphine in group M. Only the anaesthetist knew which drug was administered. The procedure was commenced once the anaesthesia reached the Th6 level. Hypotension was corrected with iv ephedrine 5-10 mg to maintain the systolic pressure above 100 mm Hg. Patients received oxygen through the face mask until extraction of the newborn (40%) and 5 U of iv oxytocin – after extraction. The Apgar score was determined at one minute and five minutes after delivery.

The study covered the period from subarachnoid administration of LA agents until 24 h after surgery; some intraoperative data were also included.

In the postoperative period, the following parameters were assessed: HR, SAP, DAP, f, SpO2 and analgesic efficacy according to VAS (0-10 range). The severity of pain was evaluated by patients on deep breaths, cough and movement. Nurses, who did not know which drug had been administered, recorded the parameters in the protocol at 2, 4, 6, 8, 12, 16, 20 and 24 h since anaesthesia induction. Moreover, the times and doses of analgesics and other agents required were recorded. The episodes of nausea and vomiting, pruritus, depth of sedation and respiratory depression (f<10) were noted down. Urine retention was not assessed due to routine catheterization of the urinary bladder.

After surgery, all patients received analgesics depending on pain sensations according to the following scheme: paracetamol – 1g iv every 6 h, ketoprofen – 100 mg iv every 12 h; the first dose of both agents was administered 2 h after anaesthesia induction (before anaesthesia subsided completely). Each patient had the PCA pump with pethidine (a single dose – 10 mg, refraction time – 10 min, max. dose for 4 h – 1.5 mg kg-1). Patients were instructed to start the pump once the pain severity exceeded VAS 3.

After 24 h, on leaving the operating room, patients completed the anonymous questionnaire. They assessed the anaesthesia method, quality of postoperative pain management according to 4-degree scale (very good, good, medium, bad), readiness to undergo such anaesthesia in future, and compared it with the previous ones, if administered.

The values with normal distribution were statistically analysed using the Student’s t-test for unrelated data. The results were presented as a mean and standard deviation. P<0.05 was considered significant.

RESULTS

The study involved 60 pregnant women aged 18-45 years, allocated to group F and M, 30 patients each. Age, body weight and height were comparable in both groups (Table 1). Three women were excluded: 2 because of unsuccessful spinal blockade and 1 due to lack of consent for the protocol.

The time between anaesthesia induction and skin incision (IIT) was comparable between the groups.

In all patients, the level of anaesthesia reached at least Th6; one group F patient and 7 group M patients reported intraoperative pain sensations, which required additional administration of iv fentanyl, 0.1-0.2 mg.

The Apgar score was similar in both groups. All newborns had 8-10 points at one minute and 10 points at five minutes.

The mean use of pethidine during the first 24 h was significantly higher in group F than in group M (p<0.001); the mean time to the first start of the PCA pump was markedly longer after morphine (Table 2). In 4 group F patients, this method was insufficient and additional doses of analgesics were used (1 woman received 590 mg of pethidine within 24 h); due to the study method, these data were not included in the statistical analysis.

The PCA opioid requirements in group F increased 2 h after the anaesthesia induction, reaching the maximum dose of 12 mg h1 at 5 h of observation (Fig. 1). At about 14 h, the requirements decreased to 3-4 mg h-1 and remained at this level until 24 h.

In group M, the use of pethidine was minimal until 3 h after induction (amongst 28 patients, the PCA pump was used only in two cases). The demands increased at 4 h, on average to 2 mg h-1, remaining at this level in the successive hours.

Considering two periods of different dosage in group F (8-12 mg h-1 and 3-4 mg h-1), pain management was compared in two time periods: 4-13 h and 14-24 h. In the former, the majority of group M patients took 0-20 mg of pethidine compared to 0-150 mg in group F. On average, the group F patients took the fourfold higher dose of pethidine. In the second period (14-24 h), the doses of pethidine were comparable in both groups, ranging from 0 to 40 mg (Table 2).

In the postoperative period, the patients received pethidine on request, every 10 min at most. If requested earlier, the demand was not fulfilled (futile administration). One group F patient demanded the drug 128 times within 7 h. In group F, futile administrations were markedly commoner compared to group M; 93% of group M patients had no more than  one administration whereas 24% of group F patients had 2 or more.

The severity of pain assessed immediately after surgery (2 h) and at the end of observation (24 h) was comparable in both groups. However, in the period between 4 and 20 h, the severity of pain was higher in group F (p <0.05) (Fig. 2).

As far as the adverse effects of drugs are concerned, the incidence of nausea and vomiting was similar in both groups. Pruritus was more often reported by group M patients (p=0.03). Respiratory depression developed in one group F patient at 2 h and 4 h after induction (SpO2 80% and 81%, respectively) and was accompanied by moderate sedation. No relevant haemodynamic disturbances were observed (Table 3).

Subjective assessment of patients after 24 h (anaesthesia, pain management, readiness to undergo such an anaesthesia in future, comparison with previous experiences) did not show significant differences between the groups.

DISCUSSION

The addition of opioids to local anaesthetics has been widely used in clinical practice for over 30 years; however, the efficacy and safety of this method are still in dispute. Some authors prefer lipophilic opioids highlighting their quick onset of action (intraoperative), analgesic effects in the early postoperative period (6 h) and  minor adverse side effects [6]. Fentanyl is recommended in the dose of 20-30 μg [4]. In the case of morphine, 50 μg does not provide analgesic effects while the dose of 200 μg induces too strong adverse effects (pruritus, nausea and vomiting) and symptoms of late respiratory depression [7, 8, 9, 10, 11]. The addition of 100 μg of morphine to the LA agent is recommended as optimal management during anaesthesia for hip alloplasty and is considered safe for the elderly [10]. The majority of authors document effective analgesic effects of this dose in the postoperative period [7, 8, 12, 13].

In our study, intraoperative analgesia in group M was insufficient in 25% of cases, which confirms the reports about the delayed onset of action of morphine (hydrophilic features of the compound) and may discourage from its routine use. If there was no intraoperative analgesia following subarachnoid administration of 0.2 mg of morphine, the addition of 10 μg of fentanyl improved radically analgesic effects [14]. It was demonstrated that morphine administered via the same route improved intraoperative analgesia compared to placebo cases; however, in 18% of patients additional analgesic therapy was required [15]. Our findings reveal a similar percentage of patients, who required additional analgesia after morphine compared to those receiving fentanyl. Other authors comparing the same fentanyl and morphine doses did not demonstrate differences in requirements for analgesics and suggested that morphine also acted intraoperatively [13].

Both opioids seem safe for newborns. There are no reports demonstrating possible effects of so low doses on the newborn children.

All our patients received the same basic pain management (paracetamol, ketoprofen), thus pethidine demands reflect the efficacy of subarachnoid opioids. In the case of fentanyl, incremental doses of pethidine (since 2 h after induction) indicate relatively short-term postoperative analgesia (ca 3-4 h).

Otherwise, the analgesic effects of morphine, decreasing the demands for pethidine, maintained for at least 13 h. Some authors assess that morphine acts for about 18 h, others – that for over 24 h [7].

The number of futile PCA administrations of pethidine was likely to evidence insufficient analgesia and was significantly higher in group F, in which the mean pain severity was also higher. This confirms other reports demonstrating that morphine provided better postoperative analgesia [13].

Pruritus was more common in group M, yet was not bothersome and did not require therapeutic interventions. The results published by other authors are comparable [8, 10], although there are reports indicating that adverse effects of morphine occur in 94% of cases [16]. The incidence of nausea and vomiting was comparable in both groups (7%). The literature data confirm our observations concerning morphine [9] or demonstrate that subarachnoid morphine does not affect the incidence of this complication [17]. The 100 μg dose of morphine seems safe considering the induction of sedation or late respiratory depression although the findings of the present study are not explicit. 

CONCLUSIONS

1. In some cases, intraoperative spinal analgesia with morphine requires additional administration of iv opioids.

2. The subarachnoid administration of 100 μg of morphine for Caesarean section provides better postoperative analgesia for 12 h compared to fentanyl.

3. Both methods of analgesia are safe and adverse side effects related to them are acceptable.

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REFERENCES

1.    Siegel T, Mayzner-Zawadzka E: Regionalna anestezja w Polsce w 2002 roku. Anaesthesiol Intensive Ther 2004; 36: 89-96.

2.    Duck Hwan Choi, Hyun Joo Ahn, Myung Hee Kim: Bupivacaine-sparing effect of fentanyl in spinal anesthesia for cesarean delivery. Reg Anesth Pain Med 2000; 25: 240-245.

3.    Kiran S, Singal NK: A comparative study of three different doses of 0.5% hyperbaric bupivacaine for spinal anaesthesia in elective caesarean section. Int J Obstet Anaesth 2002; 11: 185-189.

4.    Hamber EA, Viscomi CM: Intrathecal lipophilic opioids as adjuncts to surgical spinal anesthesia. Reg Anesth Pain Med 1999; 24: 255-263.

5.    Chan Jung Chung, Sung Hun Yun, Gi Baeg Hwang, Jung Sil Park, Young Jhoon Chin: Intrathecal fentanyl added to hyperbaric ropivacaine for cesarean delivery. Reg Anesth Pain Med 2002; 27: 600-603.

6.    Hunt CO, Naulty JS, Bader AM, Hauch MA, Vartikar JV, Datta S, Hertwig LM, Ostheimer GW: Perioperative analgesia with subarachnoid fentanyl-bupivacaine for cesarean delivery. Anesthesiology 1989; 71: 535-540.

7.    Uchiyama A, Nakano S, Ueyama H, Nishimura M, Tashiro C: Low dose intrathecal morphine and pain relief following caesarean section. Int J Obstet Anesth 1994; 3: 87-91.

8.    Abboud TK, Dror A, Mosaad P, Zhu J, Mantilla M, Swart F, Gangolly J, Silao P, Makar A, Moore J: Mini-dose intrathecal morphine for the relief of post-cesarean section pain: safety, efficacy, and ventilatory responses to carbon dioxide. Anesth Analg 1988; 67: 137-143.

9.    Milner AR, Bogod DG, Harwood RJ: Intrathecal administration of morphine for elective caesarean section. A comparison between 0.1 mg and 0.2 mg. Anaesthesia 1996; 51: 871-873.

10.    Bowrey S, Hamer J, Bowler I, Symonds C, Hall JE: A comparison of 0.2 and 0.5 mg intrathecal morphine for postoperative analgesia after total knee replacement. Anaesthesia 2005; 60: 449-452.

11.    Dahl BD, Jeppesen IS, Jorgensen H, Wetterslev J, Moiniche S: Intraoperative and postoperative analgesic efficacy and adverse effects of intrathecal opioids in patients undergoing cesarean section with spinal anesthesia. Anesthesiology 1999; 91: 1919-1927.

12.    Murphy PM, Stack D, Kinirons B, Laffey JG: Optimizing the dose of intrathecal morphine in older patients undergoing hip arthroplasty. Anesth Analg. 2003; 97: 1709-1711.

13.    Sibilla C, Albertazzi I, Zatelli R, Martinello R: Perioperative analgesia for caesarean section: comparison of intrathecal morphine and fentanyl alone or in combination. Int J Obstet Anesth 1997; 6: 43-48.

14.    Connelly NR, Dunn SM, Ingold V, Villa EA: The use of fentanyl added to morphine-lidocaine-epinephrine spinal solution in patients undergoing cesarean section. Anesth Analg 1994; 78: 918-920.

15.    Abouleish E, Rawal N, Fallon K, Hernandez D: Combined intrathecal morphine and bupivacaine for cesarean section. Anesth Analg 1988; 67: 370-374.

16.    Charuluxananan S, Kyokong O, Somboonviboon W, Narasethakamol A, Promlok P: Nalbuphine versus ondansetron for prevention of intrathecal morphine-induced pruritus after cesarean delivery. Anesth Analg 2003; 96: 1789-1793.

17.    Weber EWG, Slappendel R, Gielen MJM, Dirksen R: Intrathecal addition of morphine to bupivacaine is not the cause of postoperative nausea and vomiting. Reg Anesth Pain Med 1998; 23: 81-86.

17.    Dahl BD, Jeppesen IS, Jorgensen H, Wetterslev J, Moiniche S: intraoperative and postoperative analgesic efficacy and adverse effects of intrathecal opioids in patients undergoing cesarean section with spinal anesthesia. Anesthesiology 1999; 91: 1919-27.

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Address:

*Wojciech Weigl
Szpital Kliniczny Dzieciątka Jezus
Centrum Leczenia Obrażeń
ul. Lindley’a 4, 02-005 Warszawa
tel.: 0-22 502 17 21, 0-602 262 885, fax: 0-22 502 21 03
e-mail: weiglwojtek@poczta.onet.pl

Received: 25.10.2008
Accepted: 20.01.2009.