[Delta(9)-tetrahydrocannabinol and the opioid receptor agonist piritramide do not act synergistically in postoperative pain]. / Keine synergistische Wirkung der Kombination von Delta(9)-Tetrahydrocannabinol und Piritramid bei postoperativen Schmerzen.

BACKGROUND: It is concluded from animal experiments that cannabinoid receptor and mu-opioid receptor agonists act synergistically with respect to antinociception. In order to demonstrate this effect under clinical conditions, we conducted a randomized double blind trial with patients after radical prostatectomy. PATIENTS AND METHODS: From the evening before the operation until the morning of the second postoperative day, all patients received eight oral doses of either placebo or 5 mg Delta(9)-tetrahydrocannabinol (dronabinol). Postoperatively patients had access to patient-controlled analgesia with the micro-opioid agonist piritramide for 48 h. We expected patients receiving dronabinol to require significantly less piritramide compared to patients on placebo. RESULTS: The consumption of piritramide was recorded in 100 patients after radical retropubic prostatectomy with regional lymphadenectomy. Patients in the placebo group consumed 74 mg (median), interquartile range (IQR) 44-90 mg, patients in the verum group consumed 54 mg (median) IQR 46-88 mg. The difference between groups was not statistically significant. Plasma concentrations of Delta(9)-THC were measurable in all patients in the verum group. The levels (median) were 1.5 ng/ml (IQR 0.6-2.3), 1.3 ng/ml (IQR 0.5-2.2) and 1.9 ng/ml (IQR 0.8-2.7) on the day of operation, the first and second postoperative day, respectively. CONCLUSION: We found neither a synergistic nor even an additive antinociceptive interaction between Delta(9)-tetrahydrocannabinol and the micro-opioid agonist piritramide in a setting of acute postoperative pain.

Immunomodulatory function of the 5-HT3 receptor antagonist tropisetron.

OBJECTIVE: To characterize the immune modulatory effects of 5-HT3 receptor antagonist treatment in patients with fibromyalgia, autoimmune disorders, and chronic pain. METHODS: Multiplex-assisted cytokine measurements were performed before and during treatment. Whole blood stimulation with TNF-alpha was carried out to determine the proinflammatory response induced by exogenous TNF-alpha. RESULTS: Five of nine patients clinically responded to treatment, and two had a moderate response. All patients had significantly elevated levels of T-H1 cytokines more prominent than TNF-alpha, IL-1beta, and IL-6. Treatment resulted in transient effects on peripheral monocyte counts in all but one patient, a plasma IL-1beta increase in two responder patients, and decreased T-H1 cytokines in two responder patients. Ex vivo TNF-alpha stimulation was transiently reconstituted in three responder patients to a significant level. Three patients showed a marginal reconstitutive response. CONCLUSION: 5-HT3 receptor blockade transiently affects monocyte tissue infiltration, modulates T-H1 cytokines in clinical responders as well as MIP-1beta in moderate responders, and transiently affects the ex vivo response to exogenous TNF-alpha.

[Postoperative analgesia with rofecoxib. How effective is the preoperative application of a 25 mg dose?]. / Perioperative Schmerztherapie mit Rofecoxib. Wie wirksam ist die präoperative Gabe einer 25-mg-Dosis bei muskuloskelettalen Operationen?

OBJECTIVE: The purpose of this study was to evaluate the analgesic efficacy of 25 mg rofecoxib. METHODS: In a randomized, prospective double-blind study we investigated the analgesic efficacy of 25 mg rofecoxib in 62 patients scheduled for minor trauma surgery. Patients received 2 h before induction of anesthesia either 25 mg rofecoxib (verum) orally or placebo. These applications were repeated postoperatively after 24 h. Postoperative pain intensity was measured by the numeric rating scale (NRS). All patients were allowed to order piritramid from a PCA-device (bolus 2 mg, lockout 5 min in the recovery room, 15 min on the ward) for 24 h after surgery. 10/20/30 min, as well as 1/2/4/6 h and 24 h after surgery cumulated doses of piritramid, pain scores (0-10) and side effects were recorded. RESULTS: Pain relief and cumulated doses of piritramid in both groups were comparable at all points in time. There were no significant differences in the incidence of side effects between the two groups. CONCLUSION: Preoperative application of 25 mg rofecoxib is not effective for postoperative analgesia in patients after minor trauma surgery.

Spinal hematoma: a literature survey with meta-analysis of 613 patients.

Spinal hematoma has been described in autopsies since 1682 and as a clinical diagnosis since 1867. It is a rare and usually severe neurological disorder that, without adequate treatment, often leads to death or permanent neurological deficit. Epidural as well as subdural and subarachnoid hematomas have been investigated. Some cases of subarachnoid spinal hematoma may present with symptoms similar to those of cerebral hemorrhage. The literature offers no reliable estimates of the incidence of spinal hematoma, perhaps due to the rarity of this disorder. In the present work, 613 case studies published between 1826 and 1996 have been evaluated, which represents the largest review on this topic to date. Most cases of spinal hematoma have a multifactorial etiology whose individual components are not all understood in detail. In up to a third of cases (29.7%) of spinal hematoma, no etiological factor can be identified as the cause of the bleeding. Following idiopathic spinal hematoma, cases related to anticoagulant therapy and vascular malformations represent the second and third most common categories. Spinal and epidural anesthetic procedures in combination with anticoagulant therapy represent the fifth most common etiological group and spinal and epidural anesthetic procedures alone represent the tenth most common cause of spinal hematoma. Anticoagulant therapy alone probably does not trigger spinal hemorrhage. It is likely that there must additionally be a "locus minoris resistentiae" together with increased pressure in the interior vertebral venous plexus in order to cause spinal hemorrhage. The latter two factors are thought to be sufficient to cause spontaneous spinal hematoma. Physicians should require strict indications for the use of spinal anesthetic procedures in patients receiving anticoagulant therapy, even if the incidence of spinal hematoma following this combination is low. If spinal anesthetic procedures are performed before, during, or after anticoagulant treatment, close monitoring of the neurological status of the patient is warranted. Time limits regarding the use of anticoagulant therapy before or after spinal anesthetic procedures have been proposed and are thought to be safe for patients. Investigation of the coagulation status alone does not necessarily provide an accurate estimate of the risk of hemorrhage. The most important measure for recognizing patients at high risk is a thorough clinical history. Most spinal hematomas are localized dorsally to the spinal cord at the level of the cervicothoracic and thoracolumbar regions. Subarachnoid hematomas can extend along the entire length of the subarachnoid space. Epidural and subdural spinal hematoma present with intense, knife-like pain at the location of the hemorrhage ("coup de poignard") that may be followed in some cases by a pain-free interval of minutes to days, after which there is progressive paralysis below the affected spinal level. Subarachnoid hematoma can be associated with meningitis symptoms, disturbances of consciousness, and epileptic seizures and is often misdiagnosed as cerebral hemorrhage based on these symptoms. Most patients are between 55 and 70 years old. Of all patients with spinal hemorrhage, 63.9% are men. The examination of first choice is magnetic resonance imaging. The treatment of choice is surgical decompression. Of the patients investigated in the present work, 39.6% experienced complete recovery. The less severe the preoperative symptoms are and the more quickly surgical decompression can be performed, the better are the chances for complete recovery. It is therefore essential to recognize the relatively typical clinical presentation of spinal hematoma in a timely manner to allow correct diagnostic and therapeutic measures to be taken to maximize the patient's chance of complete recovery.

[Droperidol and dimenhydrinate alone or in combination for prevention of postoperative nausea and vomiting]. / Droperidol und Dimenhydrinat alleine und in Kombination zur Prophylaxe von Ubelkeit und Erbrechen in der postoperativen Phase.

BACKGROUND: Droperidol and dimenhydrinate are inexpensive antiemetic drugs. Droperidol, especially, has been studied extensively in the past, but there are no studies that used the combination of both drugs for prevention of postoperative nausea and vomiting (PONV). Thus, the aim of this randomised controlled and double-blinded study was to evaluate the antiemetic efficacy and the side effects of such a combination therapy. METHODS: 240 inpatients undergoing ENT surgery under general anaesthesia were randomised to receive one of four antiemetic regimes: placebo, dimenhydrinate (1 mg x kg-1), droperidol (15 micrograms x kg-1), or the combination of both drugs (droperidol 15 micrograms x kg-1 + dimenhydrinate 1 mg x kg-1) was administered after induction of anaesthesia and repeated 6 hours after the first administration. For general anaesthesia a standardised technique including benzodiazepine premedication, propofol, desflurane in N2O/O2, vecuronium, and a continuous infusion of remifentanil was used. Postoperative analgesia and antiemetic rescue medication were standardised. Episodes of vomiting, retching, nausea, and the need for additional antiemetics were recorded for 24 hours. The main goal of the study was to increase the number of patients who were completely free from PONV (chi 2-test with Fisher-Yates' correction). Furthermore, the severity of PONV was analysed using a standardised scoring algorithm. RESULTS: Data of 227 patients could be analysed. The incidence of patients who suffered from PONV was 41.3% (95%-confidence interval: 29-55%) in the placebo-group. Dimenhydrinate alone reduced PONV to 34.5% (95%-CI: 22-48%). This marginal effect and the effect of droperidol (PONV: 26.4% (95%-CI: 15-40%)) could not be proven statistically, since the power of the study was too small. The combination of both drugs decreased PONV to 19.6% (95%-CI: 10-32%) and also reduced the severity of the symptoms to a clinically acceptable level. CONCLUSION: Dimenhydrinate failed to reduce the incidence and severity of PONV. The efficiency of droperidol given alone was within the ranges previously known from metaanalytic data. The combination of both drugs showed a moderate synergistic effect.

Dimenhydrinate and metoclopramide alone or in combination for prophylaxis of PONV.

PURPOSE: Dimenhydrinate and metoclopramide are inexpensive antiemetic drugs. Metoclopramide, especially, has been studied extensively in the past, but there are no studies on the combination of both drugs for prevention of postoperative nausea and vomiting (PONV). METHODS: One hundred and sixty male inpatients undergoing endonasal surgery were randomized to receive one of four antiemetic regimens in a double-blind manner: placebo, 1 mg x kg(-1) dimenhydrinate, 0.3 mg x kg(-1) metoclopramide, or the combination of both drugs was administered after induction of anesthesia. Patients received a second dose of these drugs six hours after the first administration to mitigate their short half-life. Standardized general anesthesia included benzodiazepine premedication, propofol, desflurane in N2O/O2 vecuronium, and a continuous infusion of remifentanil. Postoperative analgesia and antiemetic rescue medication were standardized. Episodes of vomiting, retching, nausea, and the need for additional antiemetics were recorded for 24 hr. The incidences of PONV were analyzed with Fisher's Exact test and the severity of PONV (rated by a standardized scoring algorithm) with the Jonckheere-Terpestra-test. RESULTS: The incidence of patients free from PONV was 62.5% in the placebo-group and increased to 72.5% in the metoclopramide-group (P = 0.54), 75.0% in the dimenhydrinate-group (P = 0.34), and 85.0% in the combination- group (P = 0.025). In the latter group, the severity of PONV was reduced compared with placebo treatment (P = 0.017; Jonckheere-Terpestra-test). CONCLUSION: Dimenhydrinate and metoclopramide were ineffective in reducing the incidence and the severity of PONV. Their combination reduced the incidence of PONV compared with placebo.

Evaluation of three risk scores to predict postoperative nausea and vomiting.

BACKGROUND: So far there are three different scores to predict postoperative vomiting (PV: Apfel et al., 1998) or postoperative nausea and vomiting (PONV: Koivuranta et al., 1997; Palazzo and Evans, 1993). All three scores used logistic regression analysis to identify and create weights for the risk factors for PV or PONV. In short, these were sex, age, history of previous PONV, motion sickness, duration of anaesthesia, and use of postoperative opioids. However, an external evaluation and a comparison of these scores has not been performed so far. METHODS: Patients undergoing a variety of surgical procedures under general anaesthesia were studied prospectively. Preoperatively, they completed a questionnaire concerning potential risk factors for the occurrence of PV or PONV implemented in the three risk scores. Balanced anaesthesia (induction agent, nondepolarising neuromuscular blocker, opioid, and inhalation agent in nitrous oxide/oxygen) was performed. No intravenous anaesthesia or any antiemetic prophylaxis was applied. Postoperatively, the patients were observed in the recovery room for the occurrence of PV and PONV and were visited twice on the ward within the 24-h observation period. Both the patients and the nursing staff were asked whether PV or PONV was present. The severity of PONV was categorised using a standardised scoring algorithm. A total of 1,444 patients was finally included into the analysis. Using information of the predicted risk for the individual patients and the actual occurrence of PV or PONV, Receiver Operator Characteristics (ROC-curves) were drawn. The area under each ROC-curve was calculated as a means of the predictive properties of each score and was compared for statistical differences. RESULTS: For prediction of PONV (any severity) the AUC-values (AUC=area under the curve) and the corresponding 95%-confidence intervals were: Apfel: 0.70 (0.67-0.72); Koivuranta: 0.71 (0.69-0.73); Palazzo: 0.68 (0.65-0.70). For prediction of PV: Apfel: 0.73 (0.71-0.75); Koivuranta: 0.73 (0.70-0.75); Palazzo: 0.68 (0.65-0.70). Thus, all three scores appeared to have a moderate accuracy as measured by the AUC. The score of Koivuranta predicts PONV (P=0.007) and also PV (P=0.002) significantly better than Palazzo's score. Furthermore, for predicting of PV the score of Apfel was also superior to Palazzo's score (P=0.005). All three scores predict PV with the same accuracy as PONV. CONCLUSION: The occurrence of PV and PONV in patients undergoing surgery under balanced anaesthesia can be predicted with moderate but acceptable accuracy using one of the available risk scores, regardless of local surgical or anaesthesiological circumstances. For clinical practice, we recommend the score published by Koivuranta, since its calculation is very simple.

Spinal epidural abscess: a meta-analysis of 915 patients.

Spinal epidural abscess (SEA) was first described in the medical literature in 1761 and represents a severe, generally pyogenic infection of the epidural space requiring emergent neurosurgical intervention to avoid permanent neurologic deficits. Spinal epidural abscess comprises 0.2 to 2 cases per 10,000 hospital admissions. This review intends to offer detailed evaluation and a comprehensive meta-analysis of the international literature on SEA between 1954 and 1997, especially of patients who developed it following anesthetic procedures in the spinal canal. In this period, 915 cases of SEA were published. This review is the most comprehensive literature analysis on SEA to date. Most cases of SEA occur in patients aged 30 to 60 years, but the youngest patient was only 10 days old and the oldest was 87. The ratio of men to women was 1:0.56. The most common risk factor was diabetes mellitus, followed by trauma, intravenous drug abuse, and alcoholism. Epidural anesthesia or analgesia had been performed in 5.5% of the patients with SEA. Skin abscesses and furuncles were the most common source of infection. Of the patients, 71% had back pain as the initial symptom and 66% had fever. The second stage of radicular irritation is followed by the third stage, with beginning neurological deficit including muscle weakness and sphincter incontinence as well as sensory deficits. Paralysis (the fourth stage) affected only 34% of the patients. The average leukocyte count was 15,700/microl (range 1,500-42,000/microl), and the average erythrocyte sedimentation rate was 77 mm in the first hour (range 2-50 mm). Spinal epidural abscess is primarily a bacterial infection, and the gram-positive Staphylococcus aureus is its most common causative agent. This is true also for patients who develop SEA following spinal anesthetics. Magnetic resonance imaging (MRI) displays the greatest diagnostic accuracy and is the method of first choice in the diagnostic process. Myelography, commonly used previously to diagnose SEA, is no longer recommended. Lumbar puncture to determine cerebrospinal fluid protein concentrations is not needed for diagnosis and entails the risk of spreading bacteria into the subarachnoid space with consequent meningitis; therefore, it should not be performed. The therapeutic method of choice is laminectomy combined with antibiotics. Conservative treatment alone is justifiable only for specific indications. Laminotomy is a therapeutic alternative for children. The mortality of SEA dropped from 34% in the period of 1954-1960 to 15% in 1991-1997. At the beginning of the twentieth century, almost all patients with SEA died. Parallel to improvements in the mortality rate, today more patients experience complete recovery from SEA. The prognosis of patients who develop SEA following epidural anesthesia or analgesia is not better than that of patients with noniatrogenic SEA, and the mortality rate is also comparable. The essential problem of SEA lies in the necessity of early diagnosis, because only timely treatment is able to avoid or reduce permanent neurologic deficits. The problem with spinal epidural abscesses is not treatment, but early diagnosis - before massive neurological symptoms occur" (Strohecker and Grobovschek 1986).

[Meta-analysis of controlled randomized studies on droperidol for prevention of postoperative phase vomiting and nausea]. / Metaanalyse kontrollierter randomisierter Studien zum Einsatz von Droperidol zur Prophylaxe von Ubelkeit und Erbrechen in der postoperativen Phase.

OBJECTIVE: Randomised, controlled trials using prophylactic droperidol to prevent postoperative nausea and vomiting (PONV) were included in a meta-analysis to estimate efficiency and dose-response of treatment. MATERIALS AND METHODS: Studies were systematically extracted from Medline, the manufacturer's database, and a supplemental search of references lists and current issues of locally available anaesthesia journals. Complete prevention of PONV defined as absence of nausea, retching, and vomiting within 6 hours (early PONV) and within 48 hours (late PONV) was chosen as the main end point. Additional information such as dose of droperidol, time and way of administration, and biometric data of the patients were extracted from each study. The pooled relative risk and the number-needed-to treat (NNT) were calculated. RESULTS: A total of 72 studies with 107 comparative subgroups were accepted for analysis according to the prospectively defined criteria. Of these sixty-nine trials reported a lower incidence of PONV with droperidol. The incidence of early and late PONV among the 5370 patients receiving droperidol was 23.4% and 38.2%, respectively. The corresponding incidence among the 3954 control patients was 40.7% and 53.9%. The relative risk for patients receiving prophylactic droperidol of suffering from early PONV was 0.58 and 0.71 for late PONV. The NNT for preventing one patient from PONV was 5.8 and 6.4 for early and late PONV, respectively. Treatment with droperidol was more effective when the baseline risk for PONV was higher than 25% for early PONV and 35% for late PONV. Under these circumstances the NNT was between 2.6 and 5.6. There was no dose response relationship for droperidol when the drug was applied in doses ranging from 0.5 to 300 micrograms.kg-1 body weight. It was not possible to derive reliable information about the incidence of side-effects of the droperidol administration. CONCLUSION: Droperidol is an effective antiemetic drug. The drug can be administered to patients with an increased risk of suffering from PONV without antiemetic prophylaxis. Since a positive dose response is lacking, droperidol should only be administered in doses of 1 mg or less.

[Validation of a risk score for prediction of vomiting in the postoperative period]. / Validierung eines Risikoscores zur Vorhersage von Erbrechen in der postoperativen Phase.

BACKGROUND: A risk score to predict postoperative vomiting was presented in a recent issue of this journal. In the present study this score was evaluated at another hospital under different surgical and anaesthetic conditions. Furthermore, we examined whether the score, which was originally designed to predict the occurrence of postoperative vomiting (POV) only, is also useful for prediction of postoperative nausea and vomiting (PONV). METHODS: The risk score was applied to 226 patients undergoing inpatient orthopaedic surgery under standardised general anaesthesia (propofol, desflurane in N(2)O/O(2), fentanyl, vecuronium, postoperative opioid analgesia). For 24 hours postoperatively, the patients were followed up for the occurrence of nausea, retching, and vomiting. Perioperatively, risk factors for POV were recorded (gender, age, smoking habits, history of previous PONV or motion sickness, duration of anaesthesia). Using these risk factors the individual risk for suffering POV was calculated for each patient. With these data two ROC-curves (for prediction of POV and PONV respectively) were constructed and the area under the ROC-curve (AUC) as a means of the prediction probabilities of the score was calculated. RESULTS: The incidence of POV as predicted by the score (22,8%) fits well to the actual incidence of this event (19,5%). The score predicts the occurrence of POV significantly better than can be expected by a random estimation. In spite of different surgical and anaesthetic conditions, the accuracy of the prediction in the present dataset was not significantly different from that reported by the authors of the scores in their validation set. Furthermore, the prediction properties for POV (AUC: 0,73) were not different from the prediction of PONV (AUC: 0,72). CONCLUSION: The present risk score provides valid prognostic results even under modified surgical and anaesthetic conditions, and, thus, may obviously be applied to other institutions. Furthermore our results support the hypothesis, that individual risk factors rather than the type of surgery or anaesthetic management have a major impact on the occurrence of POV and PONV.

[Dimenhydrinate and metoclopramide for prevention of nausea and vomiting following septorhinoplasties in women]. / Dimenhydrinat und Metoclopramid zur Prophylaxe von Ubelkeit und Erbrechen nach Septorhinoplastiken bei Frauen.

OBJECTIVES: Dimenhydrinate and metoclopramide are inexpensive antiemetic drugs. Metoclopramide, especially, has been studied extensively in the past, but there are no studies that used the combination of both drugs for prevention of postoperative nausea and vomiting (PONV). METHODS: 120 female inpatients undergoing endonasal surgery were randomised to receive one of four antiemetic regimes: placebo, dimenhydrinate (1 mg x kg-1), metoclopramide (0.3 mg x kg-1), or the combination of both drugs (1 mg x kg-1 + 0.3 mg x kg-1) were administered intravenously after induction of anaesthesia and repeated 6 hours after the first administration. For general anaesthesia a standardised technique including benzodiazepine premedication, propofol, desflurane in N2O/O2 vecuronium and a continuous infusion of remifentanil was used. Postoperative analgesia (diclofenac or metamizole supplemented with piritramide) and antiemetic rescue medication (dolasetron and droperidol) were standardised. Episodes of vomiting, retching, nausea, and the need for additional antiemetics were recorded in the recovery room and 2, 5, 8, and 24 hours after surgery. The main goal of the study was to increase the number of females staying completely free from PONV (Chi 2-test). Furthermore, the severity of PONV was analysed, using a standardised scoring algorithm. RESULTS: There were no differences between the two groups with regard to biometric data and distribution of risk factors for developing PONV. In all four groups nearly the similar number of patients stayed completely free from PONV: Placebo: 60.7%, metoclopramide: 66.7%, dimenhydrinate: 64.3%, combination: 64.4% (differences not significant). There was also no difference in the severity of nausea and emetic sequel. DISCUSSION: In females undergoing endonasal surgery under propofol-desflurane-remifentanil anaesthesia the incidence of PONV is about 40%. In this setting, both metoclopramide and dimenhydrinate were ineffective to reduce the incidence and the severity of PONV. The combination of both drugs revealed no additional synergistic effect.

[Dolasetron, droperidol and a combination of both in prevention of postoperative nausea and vomiting after extracapsular cataract extraction under general anesthesia]. / Dolasetron, Droperidol und die Kombination beider Substanzen zur Prophylaxe von Ubelkeit und Erbrechen nach extrakapsulären Kataraktextraktionen in Allgemeinanästhesie.

BACKGROUND: Both, droperidol and the new 5-HT3-antagonist (e.g. dolasetron) are effective drugs in the prevention of postoperative nausea and vomiting (PONV). It was the aim of this prospective double blind placebo controlled study to determine the efficacy of low-dose droperidol, dolasetron, and a combination of both drugs in the prevention of PONV after extracapsular cataract extraction. METHODS: 148 inpatients undergoing cataract surgery were stratified according to gender and then randomised to receive one of four antiemetic regimens: placebo, droperiodol (10 micrograms x kg-1), dolasetron (12.5 mg), or the combination of both drugs (10 micrograms x kg-1 + 12.5 mg). The drugs were administered intravenously 5-10 minutes before the end of anaesthesia. General anaesthesia and the perioperative management of the patients were standardised: benzodiazepine premedication, induction with etomidate, alfentanil and mivacurium. Maintenance using desflurane in N2O/O2, and a continuous infusion of mivacurium was used. Postoperative analgesia (diclofenac or paracetamol) and antiemetic rescue medication (dimenhydrinate and metoclopramide) was standardised. Nausea, episodes of vomiting, retching and the need for additional antiemetics were recorded for 24-hours. The severity of PONV was categorised using a standardised scoring algorithm. The main aim of the study was the number of patients who stayed completely free from PONV. RESULTS: There were no differences between the two groups with regard to biometric data, type of surgery, and distribution of risk factors for developing PONV. In all three treatment groups significantly less patients suffered from PONV (placebo: 66%; droperidol: 89%, dolasetron: 92%, combination: 89%; p = 0.011). Furthermore, the severity of PONV was reduced (p = 0.012). CONCLUSION: Low-dose droperidol and dolasetron are equally effective to reduce the incidence of PONV after cataract surgery under general anaesthesia. The combination of both drugs revealed no additional effect.

Dimenhydrinate for prevention of post-operative nausea and vomiting in female in-patients.

Dimenhydrinate is an inexpensive antihistaminic drug, that is frequently used as an anti-emetic during anaesthesia. The popularity of the drug is contrasted by the lack of modern studies concerning its efficacy in reducing the incidence of post-operative nausea and vomiting. Thus, dimenhydrinate was compared with placebo in this prospective, randomized, double-blind study. One hundred and thirty-three female in-patients were studied. They were stratified according to the type of surgery (laparoscopic cholecystectomy, thyroid resection or knee arthroscopy) to ensure an homogeneous distribution in both groups. General anaesthesia was induced with etomidate, fentanyl, vecuronium and maintained with enflurane in N2O/O2. Neuromuscular block was reversed with pyridostigmine/atropine. Patients in the dimenhydrinate group (n = 67) received 62 mg dimenhydrinate intravenously after induction of anaesthesia. Placebo patients (n = 66) received saline. Administration of dimenhydrinate (and placebo) was repeated three times during the 48-h study to mitigate the short half-life of the drug. Post-operative analgesia and anti-emetic rescue medication was standardized. Episodes of vomiting, retching and the need for additional anti-emetics were recorded. Nausea was assessed using a 10-cm visual analogue scale. Post-operative nausea and vomiting was rated as 'none', 'mild', 'moderate' and 'severe' using a fixed scoring algorithm. There were no differences between the two groups with regard to biometric data, type of surgery and distribution of risk factors for developing post-operative nausea and vomiting. In the dimenhydrinate group, more patients remained completely free from post-operative nausea and vomiting compared with placebo (dimenhydrinate: 38.8%; placebo: 15.1%; P = 0.004). The incidence of severe post-operative nausea and vomiting was also reduced from 39.4% to 14.9%. No relevant side effects were observed. Intra-operative dimenhydrinate, followed by three further administrations after surgery, reduces the incidence and the severity of post-operative nausea and vomiting without side effects. However, there still remained an unacceptable high number of patients who were not prevented completely from experiencing post-operative nausea and vomiting.

Droperidol-supplemented anaesthesia decreases post-operative nausea and vomiting but impairs post-operative mood and well-being.

Post-operative nausea and vomiting is distressing for patients and can cause dissatisfaction and impaired well-being in the post-operative period. This study examined the question whether the reduced incidence of post-operative nausea and vomiting inevitably translates into improved clinical status and well-being. In this context high doses of droperidol were investigated. On the one hand, droperidol is known to be a powerful anti-emetic, but on the other hand there is concern about psychological effects, both in the pre- and the post-operative period. In this prospective randomized double-blinded study, droperidol (5-7.5 mg) was compared with midazolam (5-7.5 mg) used to supplement fentanyl-N2O based anaesthesia, with respect to post-operative mood and well-being using a psychological questionnaire (Bf-S-test). Furthermore, the incidence of post-operative nausea and vomiting was recorded. Out of 160 patients undergoing thyroidectomy and laparoscopic cholecystectomy, data from 150 patients were analysed. The administration of droperidol significantly lowered the incidence of post-operative nausea and vomiting from 77.8% to 55.1% compared with midazolam (P = 0.0059; chi 2-test). Although post-operative nausea and vomiting is an independent risk factor for post-operative discomfort and bad mood, patients receiving droperidol showed impaired well-being 6 h after surgery. Well-being scores returned to pre-operative base-line values and did not differ between the two groups 24 and 48 h post-operatively. The reduced incidence of post-operative nausea and vomiting achieved with high dose droperidol does not equate with increased post-operative well-being. It is an important point at issue to decide whether smaller doses of droperidol that are commonly used for anti-emetic therapy are free of these side effects.

Changes in gastric intramucosal pH following mesenteric traction in patients undergoing pancreas surgery.

BACKGROUND/AIM: During major abdominal surgery, mesenteric traction (MT) may result in hemodynamic instability mainly due to endogenous prostacyclin release. Gastric intramucosal pH (pHi) and PiCO2 are indicators of splanchnic tissue perfusion with a predictive value for the postoperative outcome. We investigated the influence of MT on gastric pHi and on postoperative outcome in patients undergoing pancreas surgery. METHODS: Forty-six consecutive patients scheduled for pancreas surgery were investigated. We registered hemodynamics and pHi by gastric tonometry and documented postoperative outcome (complications, hospital stay). Baseline data (T0) were recorded after skin incision. Further assessments followed 30, 60 and 120 min after intentional MT (T1-3) and at the end of surgery (T4). RESULTS: Thirty-three patients demonstrated a decrease in mean arterial pressure (MAP) following MT, whereas 13 patients showed entirely stable hemodynamics. The significant reduction in MAP in patients with an MT response was not associated with changes in pHi as compared to patients with no response (stable MAP) (T0 7.34 +/- 0.08 vs. 7.35 +/- 0.06; T1 7.34 +/- 0.05 vs. 7.32 +/- 0.07; T2 7.32 +/- 0. 05 vs. 7.31 +/- 0.08; T3 7.32 +/- 0.05 vs. 7.32 +/- 0.07; T4 7.26 +/- 0.1 vs. 7.27 +/- 0.08; mean +/- SD, MT response vs. no response). Neither MT response nor gastric intramucosal acidosis as evidenced by a pHi <7.32 at the end of surgery predicted postoperative complications or longer hospital stay. CONCLUSION: No deterioration of gastric pHi was found, which could reflect acceptable splanchnic perfusion and oxygenation despite systemic blood pressure reactions in patients experiencing an MT response.

Droperidol and dimenhydrinate alone or in combination for the prevention of post-operative nausea and vomiting after nasal surgery in male patients.

Droperidol and dimenhydrinate are inexpensive antiemetic drugs. Droperidol, especially, has been studied extensively, but there are no studies on the combination of both drugs for prevention of post-operative nausea and vomiting. One hundred and forty male hospitalized patients undergoing nasal surgery were randomized to receive one of four anti-emetic regimes: placebo, dimenhydrinate (1 mg kg-1), droperidol (15 micrograms kg-1), or the combination of both drugs (droperidol 15 micrograms kg-1 + dimenhydrinate 1 mg kg-1) administered after induction of anaesthesia. Patients in the dimenhydrinate-group and the combination-group received a second dose of dimenhydrinate 6 h after the first administration to mitigate the short half-life of the drug. For general anaesthesia a standardized technique, including benzodiazepine premedication, propofol, desflurane in N2O/O2, vecuronium, and a continuous infusion of remifentanil, was used. Post-operative analgesia and anti-emetic rescue medication were standardized. Episodes of vomiting, retching, nausea, and the need for additional anti-emetics were recorded for 24 h. The main endpoint of this study was the number of patients who were completely free of post-operative nausea and vomiting (Fisher's Exact Test). Furthermore, the severity of post-operative nausea and vomiting was analysed using a standardized scoring algorithm. The incidence of patients completely free of post-operative nausea and vomiting was 62.9% in the placebo-group, 77.1% in the dimenhydrinate-group (P = 0.21), and 82.9% in the droperidol-group (P = 0.07). This increased to 94.3% in the combination-group (P = 0.0015). In all three treatment groups the severity of post-operative nausea and vomiting was reduced significantly compared with placebo treatment (P = 0.0003). The incidence of side effects was similar in the four groups. Dimenhydrinate was ineffective in reducing the incidence of post-operative nausea and vomiting and droperidol only reduced the severity of post-operative nausea and vomiting. However, the combination of both drugs significantly reduces the incidence of post-operative nausea and vomiting when compared with placebo treatment.

Magnetic resonance epidurography with gadolinium-DTPA.

The aim of this study was to evaluate and describe MRI epidurography as a new imaging tool. Five volunteers and one patient were investigated with MR epidurography after injection of 20 ml Gd-DPTA solution (1:250/1 ml Gd-DPTA/250 ml normal saline). Magnetic resonance epidurography is possible. With fat-suppression techniques, the contrast between Gd-DPTA solution in the epidural space and surrounding soft tissue proved adequate. Using the multiplanar capability of MRI with MR epidurography coronal and sagittal projections similar to conventional epidurography, axial slices comparable to CT epidurography can be obtained. Magnetic resonance epidurography is superior to conventional and CT epidurography. Presently, due to high costs as compared with conventional and CT epidurography, MRI is not suitable for the routine monitoring of peridural catheters, but it may have a place in the future with decreasing costs for MRI and for the evaluation of patients with spine pathology, especially in describing epidural processes.

Vasopressor hormone response following mesenteric traction during major abdominal surgery.

BACKGROUND: We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI2) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. METHODS: In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGF1 alpha (stabile metabolite of PGI2), TXB2 (stabile metabolite of thromboxane A2) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. RESULTS: Following MT, arterial hypotension occurred along with a substantial PGI2 release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF1 alpha (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P = 0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB2 (164 (87) vs. 58 (1) ng/L, P = 0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P = 0.001), AVP (41 +/- (18) vs. 12 (7) ng/L, P = 0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. CONCLUSION: Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI2 release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A2, presumably contributing to hemodynamic stability within 30 min after MT.

[Results of a survey of anesthetists on postoperative nausea and vomiting]. / Ergebnisse einer Umfrage unter Anästhesisten zum Thema Ubelkeit und Erbrechen in der postoperativen Phase.

OBJECTIVE: Although an increasing number of studies concerning postoperative nausea and vomiting (PONV) have been performed, we do not know, what anaesthesiologists think about this problem and how they handle it in their daily routine. METHODS: A survey was performed involving anesthesiologists at 30 institutions of different size. 474 out of 1000 questionnaires were returned. RESULTS: When asked what kind of general anaesthesia they prefere in a woman at a very high risk to suffer PONV, the following answers were obtained: anaesthesia induction with propofol (78%), thiopentone (17%), etomidate (5%). Maintenance of anaesthesia with an inhalation anesthetic (44%) or with propofol (44%). The remaining 14% would use a combination of these techniques (6%) or neuroleptanaesthesia with droperidol (5%) or midazolam (1%). Only 10% of the respondants would omit nitrous oxide. There is no consensus about the optimal amount of intraoperative opioids. Fentanyl, alfentanil, and sufentanil are rated to contribute equally to the occurence of PONV, whereas opioids used for postoperative analgesia are thought to have substantial differences: piritramid is rated to be much less emetogenic than tramadol and morphine. 70% advocate routine antiemetic prophylaxis for high-risk patients (most often mentioned risk factors were: female sex: 85%, obesity: 81%, high doses of intraoperative opioids: 72%) and 23% administrate antiemetics even for all patients. Ondansetron and droperidol are suggested to be superior to metoclopramide, triflupromazine, dimenhydrinate, and transdermal scopolamine. However, metoclopramide is the drug of first choice for more than 50% of the respondants followed by droperidol, whereas only 29% use ondansetron as a first line drug. An unexpected high number of anaesthesiologists (13%) have experience with non-pharmacological methods for prophylaxis and treatment of PONV. Acupuncture/acupressure (10%) was most often mentioned. CONCLUSION: A great majority (93%) stated, that PONV is a relevant problem, that still remains unsolved. This proofs the need for further controlled studies.

Therapeutic suggestions given during neurolept-anaesthesia decrease post-operative nausea and vomiting.

A double-blind randomized study was performed in 100 patients undergoing thyroidectomy to evaluate the effect of positive therapeutic suggestions made during neurolept-anaesthesia. The classic droperidol-fentanyl-N2O technique was used as these drugs preserve the neurophysiological functions required to process the information in the therapeutic suggestions given during general anaesthesia. Patients in the suggestion group heard positive non-affirmative suggestions during the whole operation. An autoreverse tape player was used. The control group listened to an empty tape. Both groups were comparable with respect to demographic variables, anaesthetic technique, drug dosage, duration of anaesthesia and surgery. Patients in the suggestion group suffered significantly less from post-operative nausea or vomiting (suggestion: 47.2% vs. control: 85.7%) and required less anti-emetic treatment (suggestion: 30.6% vs. control: 68.6%). We conclude that therapeutic suggestions heard during neurolept-anaesthesia are processed and decrease post-operative nausea and vomiting in patients after thyroidectomy.