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UNLABELLED Two identical, randomized, double-blind, placebo-controlled studies enrolled 2061 adult surgical outpatients at high risk of postoperative nausea and vomiting (PONV) to compare i.v. ondansetron 4 mg with droperidol 0.625 mg and droperidol 1.25 mg for the prevention of PONV. The antiemetic drugs or placebo were administered i.v. 20 min before the induction of anesthesia with a barbiturate compound, followed by maintenance with N2O/isoflurane/enflurane. Nausea, emetic episodes, adverse events, and patient satisfaction were analyzed for the 0 to 2 h and 0 to 24 h postoperative periods. In the 0 to 2 h postoperative period, there was a complete response (no emesis or rescue antiemetic) in 46% of subjects given placebo (P < 0.05 versus antiemetic groups), in 62% given ondansetron, in 63% given droperidol 0.625 mg, and in 69% given droperidol 1.25 mg (P < 0.05 versus ondansetron). In the 0 to 24-h postoperative period, there were no significant differences in complete response between the ondansetron and droperidol 0.625 or 1.25 mg groups; all groups remained superior to placebo. The proportion of patients without nausea during the 0 to 24 h postoperative period was greater in the antiemetic groups compared with the placebo group; however, droperidol 1.25 mg was more effective than ondansetron 4 mg or droperidol 0.625 mg (43% vs 29% or 29%, respectively). Headache incidence was higher in the ondansetron group compared with either droperidol group. Patient satisfaction scores did not differ significantly among antiemetic treatment groups, although all were superior to placebo. In conclusion, all antiemetic treatment regimens were superior to placebo for the prevention of PONV in the immediate postoperative period; however, droperidol 1.25 mg was more efficacious than ondansetron during the early recovery period (0-2 h). There were no significant differences between ondansetron and either droperidol dose for emesis prevention during the 0 to 24 h postoperative period. IMPLICATIONS More than 2000 patients at high risk of postoperative nausea and vomiting were given either placebo, ondansetron 4 mg, or droperidol 0.625 mg or 1.25 mg i.v. before the administration of general anesthesia. After surgery, the incidence of nausea, vomiting, medication side effects, and patient satisfaction were evaluated for 24 h. Droperidol 0.625 or 1.25 mg i.v. compared favorably with ondansetron 4 mg i.v. for the prevention of postoperative nausea and vomiting after ambulatory surgery.

Pain is a complex phenomenon that is influenced by physical, psychological, emotional and social factors. Nonsteroidal anti-inflammatory drugs (NSAIDs) play a fundamental role in the management of acute pain and are considered a first line option in the management of mild to moderate pain. When pain is severe, drugs such as NSAIDs plus opioids form the cornerstone of multimodal, or combination, analgesia. NSAIDs act peripherally by inhibiting prostaglandin synthesis and thereby preventing the sensitisation of tissues to other pain-generating mediators such as histamine, serotonin (5-hydroxytryptamine; 5-HT) and bradykinin. The efficacy of the NSAID ibuprofen, a propionic acid derivative, in the management of pain has been reported to be equivalent or superior to that of aspirin, propoxyphene or paracetamol (acetaminophen) with codeine. The incidence of adverse events with ibuprofen is low and this agent is better tolerated than aspirin, indomethacin and phenylbutazone. Ibuprofen has been reported to cause less gastric and duodenal injury than aspirin. Ibuprofen arginine is a new oral formulation of ibuprofen. Arginine, a nonessential amino acid, appears to improve the pharmacokinetic profile of ibuprofen by enhancing its rate of absorption. Ibuprofen arginine has been evaluated in a number of acute pain states. In one study, ibuprofen arginine demonstrated a significantly earlier onset of pain relief than ibuprofen alone in patients with osteoarticular pain. The analgesic efficacy of oral ibuprofen arginine 400mg has been reported to be similar to that of intramuscular ketorolac 30mg in the treatment of pain after caesarean section and in patients with moderately severe pain after inguinal hernia repair. Preoperative administration of oral ibuprofen arginine 400mg may also prove to be a useful alternative to oral naproxen sodium 550mg in the prophylaxis of pain associated with dental surgery, and may be considered as a treatment option in patients with recurrent tension-type headache. In addition, ibuprofen arginine may have a role in the management of pain associated with abortion and migraine headaches, clinical conditions in which it has been shown to have an analgesic effect significantly superior to that of placebo. In summary, because of its enhanced pharmacokinetic characteristics and more rapid therapeutic effect, ibuprofen arginine appears to be useful in clinical conditions requiring fast pain relief.

Butscher describes a common-sense approach to pain management which is simple, safe and effective. A wide variety of national and international organization devoted to the management of pain have universally adopted these simple measures. Current guidelines advocate both regular dosing and rescue analgesia. These guidelines were produced by an army of international experts and have been available for a decade. Although the information is widely published, it is rarely adopted in clinical practice. It is any wonder that leaders in the field of pain management ask: "Is education enough?" "Will guidelines make a difference?" They continue to lament the "tragedy of needless pain" and in despair they have called for "national initiatives on pain." Bonica stated so elegantly, "for nearly 30 yr I have studied the reasons for inadequate management of postoperative pain, and they remain the same...inadequate or improper application of available information and therapies is certainly the most important reason for inadequate analgesia does not require futuristic high tech solutions. In fact, as the economic crunch continues we may find that we cannot afford some of these new, improved and more expensive techniques. If we can provide safe and effective analgesia for only pennies a day, this option cannot be ignored. The new way may be the old way.

SUMMARY Renal transplantation has become a relatively common procedure that clinicians now offer to patients with an increasingly challenging array of medical problems; yet the mortality associated with anesthesia for renal transplantation remains low. Preoperative dialysis is of fundamental importance because it reverses many of the biochemical abnormalities caused by uremia. Modern anesthetic agents provide a greater margin of safety. There is no single or correct anesthetic for all patients with renal failure. With a clear understanding of the pharmacokinetics of anesthetic agents and an appreciation of the changes incurred by renal failure, a wide variety of agents can and have been used successfully. During renal transplantation, the anesthesiologist must optimize volume status, perfusion pressure, and other factors that affect the function and survival of the renal graft.

Patients want safe and effective analgesia. Our goal is to prevent postoperative pain in an efficient and cost effective manner. For most patients, the pain can be managed using simple, non-invasive and inexpensive analgesic techniques. Given the current economic climate, cost will become increasingly important. There will be financial pressure to expand the scope of ambulatory surgery. There will be pressure to discharge patients as soon as they are able to take oral medications. Outpatient analgesia is the oldest and most widespread form of patient-controlled analgesia--We already have the knowledge and the analgesics necessary to prevent postoperative pain. What we need now is logical, rational, and universal application of this information.

Nurse-administered analgesia is simple, universally accessible, and cost-effective. This route of administration must be fully explored and exploited to gain maximal analgesia at minimal cost. Combined, balanced multimodal analgesia with NSAIDs and opioids used preoperatively to prevent pain should be encouraged. Intraoperative analgesia should not consist solely of opioids, but also local anaesthetics and NSAIDs. Postoperatively, balanced analgesia should continue and when the patient is able to tolerate fluids the oral route of administration should be used. The solution to improved postoperative analgesia lies in exploitation and liberalization of traditional analgesic drugs and techniques. We do not need new pharmacology or new technology. We need to use the drugs and techniques we already have in a much more effective and efficient fashion. Anaesthetists have been at the forefront of delivering superb analgesia to patients after extensive major surgical procedures using epidural analgesia and patient-controlled analgesia. We must focus on postoperative pain management of all patients to ensure that optimal analgesia is provided throughout the institution. This requires a multi-disciplinary team of health care professionals and a multi-modal array of analgesics. This approach represents a change from current practice. Considerable time and energy has been invested in the development of the clinical practice guidelines and they deserve our consideration as we manage patients now and in the future.

Characteristics of nocturnal sleep were investigated in six patients after anesthesia and cholecystectomy and in another six after anesthesia and gastroplasty. All night polysomnographic recordings were obtained while each patient slept in a private surgical ward room through two nights before and five or six nights after operation. Anesthesia included thiopental, N2O, isoflurane, and fentanyl. Postoperative analgesia was provided with parenteral morphine. Other aspects of care were routine. Nocturnal sleep was markedly disturbed after both surgical procedures. Throughout the operative night and subsequent one or two nights, sleep was highly fragmented with the usual recurring cycles of sleep stages completely disrupted. Slow wave sleep was suppressed and rapid eye movement (REM) sleep virtually eliminated. During the following 2-4 nights, as other aspects of sleep recovered, REM sleep reappeared and then increased to greater than the preoperative amount. This increased REM sleep was marked by a heavy density of eye movement activity along with frequent patient reports of unusually distressing dreams or vivid nightmares. It is concluded that anesthesia with upper abdominal surgery leads to a severe disruption of nocturnal sleep followed by the release of highly intense REM sleep about the middle of the first postoperative week.

Electrocardiographic (ECG) abnormalities occur frequently following a subarachnoid hemorrhage and may also occur intraoperatively and postoperatively in patients undergoing neurovascular procedures. The aim of this study was to assess the relationship between ECG changes and the neurological status of the patient, the size and the location of the aneurysm, and the influence of these changes on the cardiac and neurological outcome. The preoperative ECG was analyzed in 270 patients. Forty-five patients had intraoperative Holter monitoring. An immediate postoperative ECG was recorded in 120 patients and 60 patients had three consecutive postoperative ECGs. Preoperatively, 52% of the patients had an abnormal ECG and the incidence was highest in patients with a poorer neurological status. Most of the ECG changes involved the T wave or the ST segment. Intraoperative and postoperative changes occurred in 35 and 65% of the patients, respectively, and were independent of the studied factors. There were no documented cardiac events. The presence of an abnormal preoperative ECG did not influence the neurological outcome of the patient, but fluctuating postoperative changes were associated with a worse outcome.

Epidural infusions of 10 micrograms/mL fentanyl combined with low-dose bupivacaine (0.1%) were compared with epidural infusions of fentanyl alone for postoperative analgesia after total knee joint replacement. There were no detectable differences between the two groups in analgesia (visual analogue scale ranging between 15 and 40 mm), infusion rates (which averaged 7-9 mL/h), or serum fentanyl levels (which reached 1-2 ng/mL). The incidence of side effects, including nausea, vomiting, and pruritus, was also similar. Of the patients receiving fentanyl and low-dose bupivacaine, one developed a transient unilateral motor and sensory loss, and one developed significant hypotension and respiratory depression. The addition of low-dose bupivacaine does not improve epidural fentanyl infusion analgesia after knee surgery and may increase morbidity.

Inspiratory mechanical loads were applied to the airway continuously for 5 min in healthy young adult volunteers maintained in a near steady-state of halothane anesthesia 1.1 MAC. The loads, both flow resistive and elastic in nature, had been selected to reduce the first loaded tidal volume approximately 10, 30, or 50%—these being designated “small,” “medium,” and “large” loads, respectively. The actual magnitudes of resistive load were 8 ± 1, 21 ± 3, and 48 ± 6 cmH2O.1−1s, and of elastic load 6 ± 1, 18 ± 1, and 41 ± 5 cmH2O. 1−1(means ± SEM). All loads caused an immediate reduction of ventilation proportional to the size of the load. This was followed by a gradual recovery of ventilation toward control values over approximately 2 min and then nearly stable ventilation for the rest of the loading period. Respiratory frequency was unchanged throughout. At 5 min of loading, ventilation and Pco2 had been nearly steady for 3 min and O2 uptake and CO2 output at the airway were unchanged from control, suggesting the establishment of a near steady respiratory state. With the small and medium loads of both types, ventilation and Paco2 in this near steady-state were not detectably different from control. With the large loads, however, ventilation was significantly reduced and Paco2 slightly increased. The end-expiratory position of the chest wall and the relative contributions of the rib cage and abdomen-diaphragm to ventilation, as estimated by antereroposterior chest wall magnetometers, were not consistently altered by any load. The small elastic loads reduced the “effective” intrinsic elastance at the end of the loading period. Loading did not increase the ratio of dead space to tidal volume (VD/VT) or the alveolar-arterial oxygen tension difference (P(A-a)o2). It is concluded that in healthy young humans anesthetized with halothane, steady-state compensation for inspiratory flow-resistive loads up to about 21 cmH2O.1−1s and inspiratory elastic loads up to 18 cmH2O · 1−1is virtually complete. Ventilatory compensation for these loads is due to nonchemical mechanisms, which in the case of small elastic loads reduce intrinsic elastance and thereby improve the performance of the ventilatory pump.

Nocturnal sleep was studied in eight healthy young volunteers before and after isoflurane anesthesia. All night polysomnographic recordings were obtained for seven consecutive nights from approximately 2300 to 0700 h. On the morning after the third night each subject was anesthetized with isoflurane 1.1 MAC for approximately 3 h. The stages and indices of nocturnal sleep were calculated for each night of study according to standard criteria. The effects of anesthesia on nocturnal sleep were confined to the first postanesthetic night. Slow wave sleep (Stages 3 and 4) was moderately suppressed from 16 +/- 1% to 6 +/- 1%, and Stage 2 sleep reciprocally increased from 52 +/- 2% to 60 +/- 2% (mean +/- SEM, P less than 0.05). There were no detectable changes in the sleep onset latency, the total quantity of sleep, or the proportion of rapid eye movement (REM) sleep. Anesthesia was followed by daytime napping in six of the eight volunteers. Nocturnal sleep was similar in the subjects who napped and those who did not. It is concluded that anesthesia with isoflurane leads to a modest and a transient change in the architecture of nocturnal sleep.