The continuous search for new approaches improving postoperative outcomes

For further improvements of postoperative outcome, prevention of postoperative nausea and vomiting and adequate pain control are crucial, as these two entities remain the most frequent postoperative complications and hence also most important complaints of patients after surgery. The reduction of PONV and postoperative pain will thus have a large impact on patient well-being and satisfaction.

The overall incidence of PONV after general anesthesia is still 20-30% (when no adequate prophylaxis has been administered), and can reach up to 80% in high risk patients. Occasionally, PONV can lead to aspiration pneumonia, wound dehiscence, surgical bleeding and esophageal rupture and dehydration. The real burden of PONV is the impairment of patients’ comfort. Moreover, PONV can lead to prolonged post anesthesia care unit (PACU) stay, necessitates an increase in nursing care and results in unanticipated hospital admissions following ambulatory surgery. As a result, PONV and its associated complications do increase costs.

80% of the patients experience acute postoperative pain after surgery, of which less than 50% receive adequate pain relief. Insufficient pain management might lead to clinical and psychological sequelae that can drastically reduce quality of life and impair recovery. Traditionally, opioids are still considered the gold standard for postoperative analgesia, but their use can cause clinically relevant, dose-limiting side effects including respiratory depression, sedation, constipation, itching, ileus, urinary retention and PONV. In an attempt to reduce opioid-related side effects, the concept of multi-modal analgesia for postoperative pain has been introduced.

The overall aim of this thesis was to investigate and develop new therapeutic approaches with which the incidence of the above-mentioned two major postoperative complications (i.e., PONV and pain) could be reduced and postoperative outcome be improved. We evaluated the efficacy of two established drugs (alizapride and lidocaine) and of a relatively new peripheral nerve block (quadratus lumborum block) for the prevention of PONV and treatment of postoperative pain.

We studied in a randomized placebo-controlled clinical trial whether 100 mg alizapride is non-inferior to 4 mg ondansetron for the prevention of PONV in patients undergoing laparoscopic gynecological surgery. Primary endpoint was the incidence of nausea and the incidence of vomiting on the PACU. Non-inferiority was tested separately for both outcomes. With respect to the incidence of nausea and to the incidence of vomiting during PACU-stay alizapride failed to show non-inferiority in comparison to ondansetron. Also regarding the incidence of PONV in the PACU and the overall incidence of PONV during 24 hours alizapride failed to demonstrate non-inferiority. Ondansetron-treated patients required significantly less rescue medication than placebo-treated patients. From this study, we concluded that there is no evidence that 100 mg alizapride is non-inferior in comparison to 4 mg ondansetron for the prophylaxis of PONV. 

Unfortunately, the low adherence to and the limited knowledge of clinical guidelines is a well-known medical problem.

We studied the incidence of PONV and the compliance to the departmental guidelines for the prevention of PONV in our institution in an uncontrolled before-and-after study using a quasi-experimental design. In a first audit, we investigated the compliance with the departmental algorithm for PONV prevention. The results of this audit revealed that the adherence to our institutional guidelines for PONV-prevention was very low. The results of this audit prompted us to simplify our institutional algorithm for the prophylaxis of PONV. All female patients now receive a triple prophylaxis (consisting of dexamethasone, ondansetron plus either a target controlled infusion with propofol or droperidol) and all male patients obtain double prophylaxis with dexamethasone and ondansetron. This simplification of our algorithm for the prevention of PONV resulted in a significant reduction of the PONV-incidence and in a better compliance with the algorithm.

Lidocaine is an amide local anesthetic with analgesic, anti-inflammatory and antihyperalgesic properties. Systemic lidocaine has been successfully used as a co-analgesic for the treatment of acute postoperative pain, especially in abdominal surgery.

We studied in a randomized placebo-controlled trial the effect of systemic lidocaine on postoperative pain in patients undergoing laparoscopic sterilization in day-case surgery.

Patients received an intravenous bolus injection of lidocaine 1.5 mg kg-1 at induction of anesthesia followed by a continuous infusion of 1.5 mg kg-1h-1 until 30 minutes after arrival on the PACU. The proportion of patients with a numeric rating scale >3, the mean numeric rating scales for pain and the opioid consumption could not be reduced by an intravenous lidocaine infusion. The median time to meet the criteria for hospital discharge were lower in patients receiving systemic lidocaine, a finding with statistical significance but questionable clinical relevance for which we were unable to elucidate the underlying mechanisms. Plasma levels of lidocaine measured when stopping the lidocaine infusion were all under the toxic dose of 5 µg ml-1. From this study, we concluded that systemic lidocaine shortens time to discharge readiness, but has no additional analgesic value in laparoscopic sterilization.

In addition, we studied the effect of systemic lidocaine on postoperative morphine requirements in patients undergoing posterior spinal arthrodesis in a randomized placebo-controlled trial. The patients received a bolus of lidocaine (1.5 mg kg-1) and an intravenous lidocaine infusion (1.5 mg kg-1h-1) until 6 hours after arrival on the PACU. Systemic lidocaine had no influence on morphine consumption during the first 24 postoperative hours. Regarding the numeric rating scores for postoperative pain, PONV-incidence, return of intestinal function, length of hospital stay and inflammatory properties no effect of systemic lidocaine could be shown. We concluded from this trial that systemic lidocaine has no analgesic efficacy and place in multimodal pain management in spinal surgery.

A transversus abdominis block or quadratus lumborum block is a rather new peripheral nerve block providing analgesia to the skin and muscles of the anterior abdominal wall. It is known from the literature that a quadratus lumborum block can reduce cumulative opioid consumption in the first 24 postoperative hours after laparoscopic colorectal surgery. The same effects are reported for systemic lidocaine in the literature.

We studied the superiority of a quadratus lumborum block in comparison with perioperative systemic lidocaine for postoperative analgesia after laparoscopic colorectal surgery in a randomized placebo-controlled trial. Patients received either a quadratus lumborum block preoperatively, a systemic lidocaine infusion perioperatively until four hours after arrival on the PACU or placebo. There was no significant difference between the quadratus lumborum group and the lidocaine group in morphine requirements during the first 24 hours. Significant differences were however observed for total morphine requirements on the PACU, for the total number of PCIA-boli demanded by the patients and the number of PCIA-boli delivered by the pump the first 24 postoperative hours between the three groups: Interestingly, the placebo-group received less morphine compared to the quadratus lumborum and lidocaine group. 

PONV and postoperative pain remain two important complaints with a great impact on postoperative outcome. We investigated new approaches to prevent PONV and postoperative pain. In summary, our studies revealed that these new approaches, i.e., the use of alizapride for PONV prophylaxis, the use of systemic lidocaine and the quadratus lumborum block in concepts of multimodal analgesia, had not the hypothesized efficacy. In contrast, following the introduction of the new PONV algorithm we observed an improved compliance of anesthetic care providers with the departmental PONV guidelines.