Glasgow Meeting - May 2003

REGIONAL ANESTHESIA AFFECTS PONV

Alain Borgeat, MD Balgrist University Hospital Zurich

Correspondence : Alain Borgeat, Chief of Staff Anesthesiology, Balgrist University Hospital, Forchstrasse 340, CH-8008 Zurich/Switzerland. Tel.: ++41 386 11 11 Fax.: ++41 386 16 09 E-mail: aborgeat@balgrist.unizh.ch

Anesthesia has become remarkably safe, and while death and permanent damage have become rare occurrences, other sequelae of anesthesia are gaining more importance. Perioperative nausea and vomiting (PONV) still is the most troublesome adverse event encountered in the recovery room, despite advances in prevention and treatment (1).The incidence of PONV has remained high and has a major negative impact on patient satisfaction about the overall surgical experience (2). Furthermore, the ongoing trend towards ambulatory procedures has increased the focus on PONV as its occurrence may delay discharge (3) or cause unanticipated hospital admission (4).

General anesthesia has long been considered as causing a greater frequency and severity of PONV than regional anesthetic techniques. Recent studies investigating this time-honored dictum in a controlled manner mostly, but not unanimously, confirmed it (5,6,7,8). Accordingly, considerable effort has been invested to examine etiology, define patients at risk, and outline preventive and therapeutic strategies in patients undergoing general anesthesia. Reviews dealing with PONV have discussed almost exclusively general anesthesia and largely ignored regional anesthesia (9,10). This contrasts with the increasing popularity of regional anesthesia. In France, the proportion of regional anesthesia increased from 15 to 25 % of all anesthetics administered from the year 1980 to the year 1996 (11). The number of local anesthetic and analgesic agents available for regional anesthesia has increased over the last two decades. Since the introduction of intrathecal and epidural morphine in 1979, a multitude of medications such as synthetic opioids, a2-agonists and cholinesterase inhibitors, have been introduced in an attempt to enhance the action of local anesthetics. The decision about their usefulness will not only rely on their effects on nerve blockade and pain relief, but also on their influence on side effects such as PONV.

Patients often express fear about PONV when questioned before surgery. Its importance compared to other possible postoperative sequelae varies but is generally high. (12). When questioned about issues of concern, 22% of 800 patients gave PONV the highest level of concern, compared to 34% for postoperative pain and 24% for waking up during surgery. (13).

Few studies are specifically designed to investigate PONV associated with regional anesthesia. Usually, the main observation is centered on factors describing the block, such as intensity or duration. PONV, if reported at all, is only a secondary endpoint. This implies that the number of patients studied is tailored to the need to show statistical significance regarding the primary endpoint. Mechanisms of postoperative nausea and vomiting in regional anesthesia. Several different mechanisms may play a role in causing PONV in patients who receive regional anesthesia. In a retrospective analysis, Crocker and Vandam (14) found that hypotension (systolic blood pressure < 80 mmHg), a block higher than the fifth thoracic segment, and the anesthetic mixture (e.g. addition of vasoconstrictors to the local anesthetic) increased the incidence of nausea and vomiting during spinal anesthesia. It appears that not one single mechanism is responsible for causing PONV. Several mechanisms may be active simultaneously, and the importance of each in a particular case may remain speculative.

Considerable effort has been invested to identify patients at increased risk of PONV. These studies often involve the use of elaborate statistics, and they vary in patient characteristics as well as surgical and anesthetic case mix. 

Age. 

The role of age remains unclear in general as well as mixed and regional anesthetic groups. It might be safe to speculate, therefore, that any influence of age on PONV that exists in regional anesthesia patients may be limited, but the impact of the wake state - stress - needs to be clarified. Finally, awake patients would be more likely to respond to certain medications (e.g. opioids) with nausea and vomiting.

There is more consistency regarding the influence of gender. Female patients were found to be at significantly higher risk of PONV in the studies of Apfel et al (15). Other factors, such as previous history of PONV or motion sickness, smoker/nonsmoker status or obesity have not been sufficiently investigated in patients under going regional anesthesia.

It is clear that PONV is a complex, multifactorial problem. To design and complete a study with sufficient size, controlling for all factors influencing PONV, represents a monumental task.

Carpenter et al. (16) studied 952 patients undergoing all types of procedures. They found an intraoperative rate of nausea of 18% and vomiting of 7%, but it must be noted that 12% of their patients received additional inhalational anesthesia. Comparatively high rates have been repeatedly observed in the context of major orthopedic (i.e., joint replacement) surgery and cesarean section.

Intrathecal epinephrine.

Studies (16) indicate that epinephrine may be a significant factor in PONV. The mechanism of the action in the absence of hemodynamic or block height differences remains unclear, but systemic epinephrine has been linked to increased serotonin release (17).

Intrathecal opioids.

Overall evidence points out that while all intrathecal opioids have the potential to increase the risk of PONV, they are not "created equal" in their tendency to do so. Meperidine appears to be the most harmful. Morphine, especially at higher doses, follows next. The lipophilic opioids, fentanyl and sufentanil, seem to carry the lowest risk.

The addition of clonidine to intrathecal solutions to prolong the action of local anesthetics results in no increase in PONV. There is no evidence after multiple studies, often involving patients undergoing orthopedic surgery, that the risk of PONV increases after addition of clonidine to various local anesthetics or opioids(18).

Neostigmine has recently been investigated as an adjuvant medication for spinal anesthesia. In volunteer studies, a dose-dependent increase in nausea and vomiting was observed after neostigmine administered either alone or in combination with a local anesthetic (19). Clinical experience demonstrates that the increased incidence of PONV associated with the application of spinal neostigmine outweighs its possible beneficial effect.

There is a wide range of PONV incidences reported when epidural anesthesia was administered for surgery.

The role of adding epinephrine to epidural local anesthetics is controversial. However, clinical experience suggests to avoid its use whenever possible.

Volunteer studies and clinical evidence confirm the potential of epidural opioids to induce nausea and vomiting. Morphine appears to carry the highest risk, while fentanyl or sufentanil have fewer emetic sequelae. Because of little available data, it is difficult to position meperidine in this regard.

Epidural clonidine does not provoke nausea or vomiting in volunteers (20). Overall, there is no evidence to date that could implicate epidural clonidine as a significant cause of PONV.

Experience with epidural neostigmine is limited. In an investigation randomizing 48 patients to receive 0, 1, 2, or 4 mg/kg epidural neostigmine in addition to a bupivacaine spinal anesthetic for minor knee surgery, no case of intraoperative nausea or vomiting was observed, and postoperative nausea scores did not differ between groups (21). These results will need to be corroborated by further studies before epidural neostigmine can be recommended for everyday practice.

In upper extremity analgesia, Wajima et al. (22) showed that operative axillary plexus blockade with postoperative continuous opioid-free plexus analgesia can result in complete absence of emetic sequelae. Borgeat et al. compared different opioid-free interscalene analgesic regimens with nicomorphine patient-controlled analgesia after shoulder surgery under combined interscalene and propofol-based general anesthesia. They consistently found significantly lower PONV rates in the regional analgesia groups (23,24,25). Other investigators reported higher incidences of PONV in similar settings, but differences in study design might account for this. For example, Singelyn et al. (26) administered an inhalational general anesthetic and used a sufentanilcontaining solution for plexus analgesia. The use of inhalational general anesthesia and the small study size could explain why Lehtipalo et al. (27) were unable to demonstrate a difference in PONV rates comparing opioid-free interscalene analgesia with morphine patient-controlled analgesia. For analgesia after surgery of the lower extremity during inhalational general anesthesia, Capdevila et al. (28) used a continuous femoral nerve block with a lidocaine-morphine-clonidine mixture and found a significantly reduced the incidence of PONV at 24 h compared with morphine patient-controlled analgesia. Similarly, Schultz et al. (29) reported a significant decrease in PONV rates when postoperative analgesia was administered after knee surgery by a bupivacaine continuous lumbar plexus block instead of epidural morphine. Singelyn et al. (30) could reduce PONV by 90 % providing analgesia after foot surgery by means of a popliteal catheter instead of by morphine patient-controlled analgesia. In contrast, Ganapathy et al. (31) could not detect a significant difference in PONV whether a continuous femoral block with bupivacaine or morphine patient-controlled analgesia were used after knee arthroplasty under spinal anesthesia, but the patients in the regional group required as much systemic morphine on the first day as the patients in the patient-controlled analgesia group. Continuous peripheral nerve blocks provide a promising tool to reduce PONV compared with standard analgesic techniques. Further investigations are warranted to define the appropriate indications and to find the optimal anesthetic solution to be used.

Postoperative nausea and vomiting remains a significant problem for both patients and clinicians. Most investigations of PONV have been conducted in the context of general anesthesia, but there is no evidence that fundamental differences exist regarding mechanisms and patient-related risk factors when regional anesthesia is considered. We have to admit that in the majority of the studies dealing with this question. The common assumption that regional anesthesia is associated with less PONV than general anesthesia is generally correct, although newer general anesthetic agents (e.g. propofol) have narrowed the gap. However, some procedures such as cesarean section or major orthopedic surgeries are followed by high PONV rates after regional anesthetic techniques. While nausea and vomiting are very rarely life-threatening, their impact on patients is negative enough to impose a deliberate search for the most appropriate anesthetic technique and to justify antiemetic strategies in high risk patient groups. The use of opioids in patients undergoing peripheral regional anesthesia remains controversial, but their potential to cause PONV should be taken into consideration. The continuation of regional analgesia into the postoperative period by means of catheter techniques offers a possibility of reducing PONV compared with opioidbased analgesic regimens. Indeed, in appropriate settings, these techniques can provide excellent pain control without the administration of opioids offering the best conditions to prevent PONV. In the ether era, nausea and vomiting were considered almost unavoidable companions of anesthesia. While a carefully planned regional anesthetic will not completely banish them, it offers to date the best chance not to cross their path and to avoid the "big little problem" of anesthesia. (32).

1. Hines R, Barash PG, Watrous G, O'Connor T: Complications occurring in the postanesthesia care unit: A survey. Anesth Analg 1992; 74:503-9

2. Myles PS, Williams DL, Hendrata M, Anderson H, Weeks AM: Patient satisfaction after anaesthesia and surgery: Results of a prospective survey of 10811 patients. Br J Anaesth 2000; 84:6-10

3. Pavlin DJ, Rapp SE, Polissar NL, Malmgren JA, Koerschgen M, Keyes H: Factors affecting discharge time in adult outpatients. Anesth Analg 1998; 87:816-26

4. Fortier J, Chung F: Unanticipated admission after ambulatory surgery-a prospective study. Can J Anaesth 1998; 45:612-9

5. Richardson MG, Dooley JW: The effects of general versus epidural anesthesia for outpatient extracorporeal shock wave lithotripsy. Anesth Analg 1998; 86:1214-8

6. Pusch F, Freitag H, Weinstabl C, Obwegeser R, Huber E, Wildling E: Single-injection paravertebral block compared to general anaesthesia in breast surgery. Acta Anaesthesiol Scand 1999; 43:770-4

7. Wulf H, Biscoping J, Beland B, Bachmann-Mennenga B, Motsch J: Ropivacaine epidural anesthesia and analgesia versus general anesthesia and intravenous patient-controlled analgesia with morphine in the perioperative management of hip replacement. Anesth Analg 1999; 89:111-6

8. Standl T, Eckert S, Esch ISA: Postoperative complaints after spinal and thiopentone-isoflurane anaesthesia in patients undergoing orthopaedic surgery - spinal versus general anaesthesia. Acta Anaesthesiol Scand 1996; 40:222-6

9. Watcha MF, White PF: Postoperative nausea and vomiting: Its etiology, treatment, and prevention. Anesthesiology 1992; 77:162-84

10. Biedler A, Wilhelm W: Postoperative nausea and vomiting. Anaesthesist 1998; 47:145-58

11. Clergue F, Auroy Y, Pequignot F, Jougla E, Lienhard A, Laxenaire MC: French survey of anesthesia in 1996. Anesthesiology 1999; 91:1509-20

12. Klafta JM, Roizen MF: Current understanding of patient’s attitudes toward and preparation for anesthesia: A review. Anesth Analg 1996; 83:1314-21

13. Shevde K, Panagopoulos G: A survey of 800 patients’ knowledge, attitudes, and concerns regarding anesthesia. Anesth Analg 1991; 73:190-8

14. Crocker JS, Vandam LD: Concerning nausea and vomiting during spinal anesthesia. Anesthesiology 1959; 20:587-92

15. Apfel CC, Greim CA, Haubitz I, Goepfert C, Usadel J, Sefrin P, Roewer N: A risk score to predict the probability of postoperative vomiting in adults. Acta Anaesthesiol Scand 1998; 42:495-501

16. Carpenter RL, Caplan RA, Brown DL, Stephenson C, Wu R: Incidence and risk factors for side effects of spinal anesthesia. Anesthesiology 1992; 76:909-16

17. Racke K, Schworer H: Regulation of serotonin release from the intestinal mucosa. Pharmacol Res 1991; 23:13-25

18. Dobrydnjov I, Samarutel J: Enhancement of intrathecal lidocaine by addition of local and systemic clonidine. Acta Anaesthesiol Scand 1999; 43:556-62

19. Liu SS, Hodgson PS, Moore JM, Trautman WJ, Burkhead DL: Dose-response effects of spinal neostigmine added to bupivacaine spinal anesthesia in volunteers. Anesthesiology 1999; 90:710-7

20. Curatolo M, Petersen-Felix S, Arendt-Nielsen L, Zbinden AM: Epidural epinephrine and clonidine segmental analgesia and effects on dfferent pain modalities. Anesthesiology 1997; 87:785-94

21. Lauretti GR, De Oliveira R, Reis MP, Juliao MDC, Pereira NL: Study of three different doses of epidural neostigmine coadministered with lidocaine for postoperative analgesia. Anesthesiology 1999; 90:1534-8

22. Wajima Z, Shitara T, Nakajima Y, Kim C, Kobayashi N, Kadotani H, Adachi H, Ishikawa G, Kaneko K, Inoue T, Ogawa R: Comparison of continuous brachial plexus infusion of butorphanol, mepivacaine and mepivacaine-butorphanol mixtures for postoperative analgesia. Br J Anaesth 1995; 75:548-51

23. Borgeat A, Perschak H, Bird P, Hodler J, Gerber C: Patient-controlled interscalene analgesia with ropivacaine 0.2% versus patient-controlled intravenous analgesia after major shoulder surgery. Anesthesiology 2000; 92:102-8

24. Borgeat A, Tewes E, Biasca N, Gerber C: Patient-controlled interscalene analgesia with ropivacaine after major shoulder surgery: PCIA vs PCA. Br J Anaesth 1998; 81:603-5

25. Borgeat A, Schäppi B, Biasca N, Gerber C: Patient-controlled analgesia after major shoulder surgery. Anesthesiology 1997; 87:1343-7

26. Singelyn FJ, Seguy S, Gouverneur JM: Interscalene brachial plexus analgesia after open shoulder surgery: Continuous versus patient-controlled infusion. Anesth Analg 1999; 89:1216-20

27. Lehtipalo S, Koskinen LOD, Johansson G, Kolmodin J, Biber B: Continuous interscalene brachial plexus block for postoperative analgesia following shoulder surgery. Acta Anaesthesiol Scand 1999; 43:258-64

28. Capdevila X, Barthelet Y, Biboulet P, Ryckwaert Y, Rubenovitch J, d'Athis F: Effects of perioperative analgesic technique on the surgical outcome and duration of rehabilitation after major knee surgery. Anesthesiology 1999; 91:8-15

29. Schultz P, Ankermoller E, Dahl JB, Christensen EF, Spangsberg N, Fauno P: Postoperative pain treatment after open knee surgery: Continuous lumbar plexus block with bupivacaine versus epidural morphine. Reg Anesth 1991; 16:34-7

30. Singelyn FJ, Aye F, Gouverneur JM: Continuous popliteal sciatic nerve block: An original technique to provide postoperative analgesia after foot surgery. Anesth Analg 1997; 84:383-6

31. Ganapathy S, Wasserman RA, Watson JT, Bennett J, Armstrong KP, Stockall CA, Chess DG, MacDonald C: Modified continuous femoral three-in-one block for postoperative pain after total knee arthroplasty. Anesth Analg 1999; 89:1197-1202

32. Kapur PA: The big „little problem". Anesth Analg 1991; 73:243-5