The influence of ondansetron on the analgesic effect of acetaminophen after laparoscopic hysterectomy.

The 5-HT(3) antagonists tropisetron and granisetron have been shown to block the analgesic effect of acetaminophen in healthy volunteers. To study the interaction between ondansetron and acetaminophen in women undergoing laparoscopic hysterectomy, we randomized 134 patients into three groups to receive acetaminophen-placebo (AP), acetaminophen-ondansetron (AO), or placebo-placebo (PP). One gram of intravenous acetaminophen or placebo was administered at the induction of anesthesia and every 6 h thereafter for 24 h, and 4 mg of ondansetron or placebo was administered at the end of surgery. Pain control was provided by patient-controlled analgesia (PCA)-oxycodone. Acetaminophen (as compared to placebo) in periodic doses starting at induction of anesthesia reduced the total dosage of oxycodone required over 0-24 h (P = 0.031), but ondansetron given at the end of the surgery had no impact on the analgesic effect of acetaminophen (P = 0.723). The Numeric Rating Scale (NRS) scores for pain were similar whether ondansetron or placebo was administered at the end of the surgery. Therefore, it may be concluded that in women undergoing laparoscopic hysterectomy, the administration of periodic doses of intravenous acetaminophen (as compared to placebo) starting at induction of anesthesia reduces the total dose requirement of oxycodone, and a concomitant dose of a 5-HT(3) antagonist such as ondansetron at the end of the surgery does not block the analgesic effect of acetaminophen.

Ondansetron has similar clinical efficacy against both nausea and vomiting.

Ondansetron is widely believed to prevent postoperative vomiting more effectively than nausea. We analysed data from 5161 patients undergoing general anaesthesia who were randomly stratified to receive a combination of six interventions, one of which was 4 mg ondansetron vs placebo. For the purpose of this study a 20% difference in the relative risks for the two outcomes was considered clinically relevant. Nausea was reduced from 38% (969/2585) in the control to 28% (715/2576) in the ondansetron group, corresponding to a relative risk of 0.74, or a relative risk reduction of 26%. Vomiting was reduced from 17% (441/2585) to 11% (293/2576), corresponding to a relative risk of 0.67, or a relative risk reduction of 33%. The relative risks of 0.67 and 0.74 were clinically similar and the difference between them did not reach statistical significance. We thus conclude that ondansetron prevents postoperative nausea and postoperative vomiting equally well.

Premedication with pregabalin 75 or 150 mg with ibuprofen to control pain after day-case gynaecological laparoscopic surgery.

BACKGROUND: Multimodal pain management has been suggested to improve postoperative analgesia. In this study, we evaluated the quality of analgesia in women undergoing day-case gynaecological laparoscopic surgery, after premedication with pregabalin 75 mg (P75) or 150 mg (P150), compared with diazepam 5 mg (D5). All patients were given ibuprofen 800 mg orally. METHODS: Altogether 90 consenting women were anaesthetized in a standardized fashion. Postoperative analgesia was provided by ibuprofen 800 mg twice a day with fentanyl i.v. on request in the recovery room (RR), and combination tablets with acetaminophen and codeine after the RR. The visual analogue scale (VAS) scores for pain and side-effects and the amounts of postoperative analgesics were recorded for 24 h after surgery. The areas under the curves (AUC) were calculated for the VAS scores for pain at rest, pain in motion, and pain at cough 1-8 and 1-24 h after surgery. RESULTS: The median AUC values for VAS scores for pain at rest (P=0.048) and in motion (P=0.046) 1-8 h after surgery were lower in the P150 group than that in the D5 group. The amounts of rescue analgesics or the degree of drowsiness did not differ in the three study groups. CONCLUSIONS: Analgesia was better after premedication with pregabalin 150 mg than after diazepam 5 mg, both with ibuprofen 800 mg, during the early recovery after day-case gynaecological laparoscopic surgery. Pregabalin 150 mg did not reduce the amount of postoperative analgesics required.

An open non-randomized study of recombinant activated factor VII in major postpartum haemorrhage.

BACKGROUND: Empirical off-label use of recombinant activated factor VII (rFVIIa) has been reported to be effective in some cases of severe postpartum haemorrhage (PPH). Successful management of these patients has lead to more wide-spread use of rFVIIa in less severe cases without any evidence for the advantages of its administration. METHODS: Until November 2006, we had administered rFVIIa to 38 parturients. Based on our initial experience with the first 12 patients, we prepared guidelines for the use of rFVIIa. During the existence of these guidelines, we made a retrospective comparison of the 26 women who received rFVIIa with another 22 women who were treated during the same time period without using rFVIIa. RESULTS: The total amount of blood loss was significantly higher (11.3 +/- 4.5 vs. 8.0 +/- 3.1 l), and the coagulation screen revealed significantly longer partial thromboplastin time (APTT) and prothrombin time (PT) values and significantly lower fibrinogen values in patients receiving rFVIIa. The need for red blood cells, platelets and fibrinogen concentrate was significantly higher in these women. Although the response was considered good in two-thirds of the women, several patients received rFVIIa with a poor or no response as a result of arterial bleeding. CONCLUSION: The decision to use rFVIIa resulted from a more profound haemorrhage. We did not gain any evidence to extend the use of rFVIIa into less severe cases of PPH. Furthermore, this policy would result in a profound increase in the overall costs of the treatment. Randomized placebo-controlled trials are urgently needed to optimize the use of rFVIIa in obstetric haemorrhage.

Surgical stress index reflects surgical stress in gynaecological laparoscopic day-case surgery.

BACKGROUND: Monitoring of analgesia remains a challenge during general anaesthesia. The surgical stress index (SSI) is derived from the photoplethysmographic waveform amplitude and the heart beat-to-beat interval. We evaluated the ability of SSI to measure surgical stress in patients undergoing gynaecological laparoscopy. Our hypothesis was that while keeping State Entropy (SE) at a predetermined level, SSI would be higher in patients receiving a beta-blocking agent (esmolol) than in those receiving an opioid (remifentanil) during laparoscopy. METHODS: Thirty women undergoing gynaecological laparoscopy were assigned randomly to receive esmolol (n = 15) or remifentanil (n = 15). Anaesthesia was induced with propofol and fentanyl and maintained with desflurane and nitrous oxide 50% in oxygen to keep SE at 50(5). The infusion of esmolol or remifentanil was started before laparoscopy and adjusted to keep the systolic blood pressure at -20 to +10% from the preoperative value. RESULTS: During the fentanyl phase, before surgery, both groups behaved similarly, with an increase in SSI after intubation. In the patients receiving esmolol, the SSI reacted to the initial incision (P < 0.05), and remained high after trocar insertion (P < 0.05). In patients receiving remifentanil, it did not react to the initial incision, but increased after trocar insertion (P < 0.05), and it remained lower both after incision (P < 0.05) and after trocar insertion (P < 0.05). CONCLUSION: SSI was higher in patients receiving esmolol. The index seems to reflect the level of surgical stress and may help guide the use of opioids during general anaesthesia.

Premedication with controlled-release oxycodone does not improve management of postoperative pain after day-case gynaecological laparoscopic surgery.

BACKGROUND: Controlled-release (CR) oxycodone provides an option for the prevention of postoperative pain. We designed this randomized double-blinded placebo controlled study to evaluate the control of pain after premedication with CR oxycodone 15 mg in addition to ibuprofen 800 mg orally in day-case gynaecological laparoscopic surgery. METHODS: Sixty consenting patients were anaesthetized in a standardized fashion. Postoperative analgesia was provided by ibuprofen 800 mg twice a day in combination with fentanyl i.v. in the recovery room and normal-release (NR) oxycodone orally after the recovery room. The visual analogue scale (VAS) scores for pain and side-effects, and the amounts of postoperative analgesics were recorded for 24 h after discharge from the hospital. After a statistical analysis of the original study, we extended the study to investigate another 10 patients, who received CR oxycodone 15 mg orally in an open-labelled fashion 60 min before surgery. The plasma concentrations of oxycodone were measured from samples drawn before and 2, 4, 6 and 8 h after premedication. RESULTS: The amounts of fentanyl [100 microg (0-330) in the CR oxycodone group; 125 microg (0-330) in the placebo group], NR oxycodone, or the VAS scores for pain during the first 24 h after the discharge from the hospital did not differ after the premedication with CR oxycodone or placebo. In the extension study group, the peak plasma concentration (C(max)) of oxycodone was 10.0 (4.6-14.7) ng ml(-1), indicating possibly a sub-therapeutic level. CONCLUSION: Oral premedication with CR oxycodone did not improve management of postoperative pain after day-case gynaecological laparoscopic surgery.

Response Entropy is not more sensitive than State Entropy in distinguishing the use of esmolol instead of remifentanil in patients undergoing gynaecological laparoscopy.

BACKGROUND: Monitoring of analgesia remains a challenge during general anaesthesia. Activation of Response Entropy (RE) to painful stimuli has been suggested to be a sign of inadequate analgesia. We evaluated the ability of RE to be more sensitive than State Entropy (SE) in measuring nociception in patients undergoing gynaecological laparoscopy. Our hypothesis was that while keeping SE at a predetermined level, RE would be higher in patients receiving a beta-blocking agent (esmolol) instead of an opioid (remifentanil) during a propofol/nitrous oxide anaesthesia. METHODS: Fifty-one women aged between 22-53 years were randomly assigned to receive esmolol (n=25) or remifentanil (n=26). SE was kept at 50+/-5. RE and SE were recorded at an interval of 30 s to 2 min and the areas under the RE and SE value-time curves (AUCRE and AUCSE) were calculated during the time of intubation and start of surgery as well as during the entire anaesthesia. The difference between RE and SE recordings in both groups was determined by subtracting the AUCSE from the corresponding AUCRE. Movements of the patients were recorded. RESULTS: No significant differences were detected in any of the several AUC values between the groups. The difference between RE and SE recordings was similar in both groups. Every patient in the esmolol group moved some time during the procedure interfering with surgery while no one in the remifentanil group moved. CONCLUSION: In patients undergoing gynaecological laparoscopic day-case surgery, RE seems not to be more sensitive than SE in guiding the use of opioids during general anaesthesia.

Recombinant factor VIIa for life-threatening post-partum haemorrhage.

The treatment of life-threatening post-partum haemorrhage (PPH) still remains challenging, and hysterectomy may be required to control the bleeding. We present 12 cases of severe PPH treated with recombinant factor VIIa (rFVIIa). We briefly describe the causes of the haemorrhage and the medical and surgical interventions before rVIIa administration. In 11 women there was a partial or good response to rFVIIa administration, while in one there was no response. In the four women undergoing a subsequent selective arterial embolization, the bleeding was significantly reduced although not completely stopped. From our experience with these 12 cases, and from previously reported cases, the use of rFVIIa may be of benefit in life-threatening PPH. However, treatment with rFVIIa, in addition to standard surgical and medical interventions, may not be definitive in every patient and a selective arterial embolization may be needed.

Influence of the injection site (L2/3 or L3/4) and the posture of the vertebral column on selective spinal anesthesia for ambulatory knee arthroscopy.

BACKGROUND: We tested the hypothesis that selective spinal anesthesia for ambulatory knee arthroscopy can be accomplished with a small dose of bupivacaine at the L3/4 interspace with or without a head-down tilt of 5 degrees when the patients were in the lateral decubitus position. METHODS: In this double-blind study, 123 patients were randomly allocated to receive spinal anesthesia with 4 mg of hyperbaric bupivacaine inserted at either the L2/3 interspace, while the vertebral column was kept horizontal (L2/3 group), or the L3/4 level, with the vertebral column horizontal (L3/4H) or tilted 5 degrees head-down (L3/4T). At 7 min, an additional head down tilt was used in all groups if the sensory block was inadequate. RESULTS: In the L3/4T group the sensory block (Th8) reached a significantly higher level 30 min after spinal injection, compared with both the L2/3 (Th10) and L3/4H (Th11) groups. In the L3/4H group, 39% of the patients needed an additional tilt for 3 min at 7 min, compared with 10% (P=0.004) in the L3/4T group. Sacral block developed later and recovered faster (P<0.05) in the L3/4T group compared to the L3/4H group. Home-readiness was achieved equally fast in all groups. CONCLUSION: When producing selective spinal anesthesia, the posture of the vertebral column is a major determinant of both sensory and motor segments to be blocked. A 4-mg dose of hyperbaric bupivacaine at the L3/4 interspace with a 5 degrees head-down tilt of the vertebral column for 6 min is recommended for knee arthroscopy.

Ondansetron does not prevent pruritus induced by low-dose intrathecal fentanyl.

BACKGROUND: Addition of an opioid to low-dose spinal anesthesia with bupivacaine improves the quality and success of anesthesia. However, the intrathecal fentanyl-induced pruritus is as high as 75%. We hypothesized that after administration of 4 or 8 mg of prophylactic IV ondansetron, the incidence of pruritus induced by low-dose intrathecal fentanyl would be significantly lower than after placebo. METHODS: In this double-blind study, 90 outpatients undergoing knee arthroscopy received 3 mg of bupivacaine + 10 micro g fentanyl intrathecally. Before spinal puncture, the patients received randomly either saline (P) or ondansetron 4 mg (O4) or 8 mg (O8) IV. They were asked about pruritus frequently, and they estimated its severity on a scale of 0-10. RESULTS: There was no difference in the incidence of pruritus between the three groups: pruritus occurred in 17 (57%), in 21 (75%) and in 19 patients (70%) in P, O4 and O8 groups, respectively. The pruritus was mostly mild. Four patients in the placebo group, three in the O4 and four patients in the O8 groups considered it severe. One patient in each group requested treatment for pruritus; after IV naloxone their pruritus was relieved. Neither time to pruritus nor duration of pruritus differed between the groups. One patient in each group developed a long-lasting (>10 h) pruritus. CONCLUSIONS: After prophylactic administration of 4 or 8 mg of ondansetron IV, the incidence, duration and severity of pruritus were similar to placebo. Ondansetron does not prevent pruritus induced by low-dose intrathecal fentanyl.

The results of 15 years of consistent strategy in treating antenatally suspected pelvi-ureteric junction obstruction.

OBJECTIVE: To determine how to select patients for surgery among those with antenatally detected pelvi-ureteric junction (PUJ) obstruction. PATIENTS AND METHODS: The study comprised 100 consecutive children with antenatally detected suspected unilateral PUJ obstruction and a normal contralateral kidney. The correct diagnosis was made using postnatal ultrasonography, intravenous urography and renal scintigraphy, the last also being used for the follow-up. RESULTS: Four patients had poor function in the hydronephrotic kidney, treated in three by nephrectomy; 61 had normal function in the hydronephrotic kidney, with 49 followed for 1-10 years with no change in kidney function and no symptoms. Twelve patients in this group had later surgery (at 0.7-8 years old) because of pyelonephritis (four), pain and/or renal functional impairment (eight, three of whom had normal function afterward). Thirty-five patients had moderately impaired function of the hydronephrotic kidney; 29 had primary surgery at a median age of 4 months. The median hydronephrotic renal function increased from 32% before to 42% after surgery, with 15 kidneys having normal function. In one other patient the kidney was lost before surgery. Five other patients were initially treated conservatively and the hydronephrotic renal function increased from 32% to 35% at the 1-year follow-up, significantly less than in the surgical group. The overall operative complication rate was 4%. CONCLUSIONS: With our management programme more than half the patients can avoid surgery in childhood. Although the follow-up was intense there was moderate and irreversible functional kidney deterioration in 5%. In contrast, after successful reconstructive surgery, only a few follow-up procedures causing possible discomfort to the child are needed in most. The risk of surgical complications cannot be neglected. The present results are useful for advising parents deciding whether their antenatally detected hydronephrotic child should undergo surgery or not.

Intrathecal hyperbaric bupivacaine 3 mg + fentanyl 10 microg for outpatient knee arthroscopy with tourniquet.

BACKGROUND: Combination of local anesthetic and opioid enables the use of less spinal anesthetic and increases the success of anesthesia. Intrathecal opioid does not prolong motor recovery and thus should not delay discharge home. We hypothesized that 3 mg of hyperbaric bupivacaine with 10 microg of fentanyl permits fast-tracking or shorter stay in post anesthesia care unit (PACU), and earlier discharge home, compared with 4 mg of hyperbaric bupivacaine. METHODS: In this double-blind study, 100 outpatients undergoing knee arthroscopy received randomly either 4 mg of bupivacaine (B4) or 3 mg of bupivacaine + 10 microg fentanyl (B3F) intrathecally. The volume of 0.8 ml was injected at the L2/3 interspace over a 2-min period. A lateral decubitus position was maintained for 10 min. The sensory block was recorded by using thermal stimuli, and motor block was assessed according to a modified Bromage scale. Fast-tracking criteria were complete recovery of motor block, sensory block Th12 or lower and stable vital signs. RESULTS: One block (1%) failed. Motor recovery was faster in the B3F group: 60% of the patients recovered in 80 min or less compared with 28% in group B4 (P = 0.002). The PACU-time was shorter: 36 (10-103) vs. 55 (10-140) min, respectively (P = 0.005). Seventeen (B3F) vs. nine patients (B4) could bypass PACU (NS). Time to discharge home was similar in both groups. In the B3F group, 75% of the patients developed pruritus. CONCLUSION: Both solutions produced reliable spinal anesthesia for outpatient knee arthroscopy. The PACU-time was shorter in the bupivacaine-fentanyl group, but both groups reached home-readiness equally.

Oral ondansetron, tropisetron or metoclopramide to prevent postoperative nausea and vomiting: a comparison in high-risk patients undergoing thyroid or parathyroid surgery.

BACKGROUND: Oral antiemetic prophylaxis may be a practical alternative to intravenous administration. Intravenous ondansetron and tropisetron prevent postoperative nausea and vomiting (PONV) at least as efficiently as traditional antiemetics, droperidol and metoclopramide. We tested the hypothesis that the incidence of PONV after oral ondansetron or tropisetron prophylaxis is lower compared with metoclopramide among high-risk patients. METHODS: In a prospective, double-blind study we studied 179 high-risk patients who received either ondansetron 16 mg, tropisetron 5 mg, or metoclopramide 10 mg orally 1 h before the operation. A standard general anesthetic technique and postoperative analgesia were used. The incidence of PONV and the need for rescue antiemetic medication was recorded for 24 h. RESULTS: In the postanesthesia care unit, the incidence of PONV was lower after premedication with tropisetron compared with ondansetron and metoclopramide (15%, 32% and 39%, respectively). The incidence of PONV during 0-24 h was the same in each group (68%, 58% and 75% in the ondansetron, tropisetron and metoclopramide group, respectively), but the incidence of vomiting was significantly lower after ondansetron (34%) and tropisetron (22%) prophylaxis compared with metoclopramide (53%). The need for additional antiemetics was significantly lower after tropisetron prophylaxis compared with metoclopramide. Patient satisfaction was significantly higher after tropisetron than after metoclopramide. CONCLUSIONS: In the initial period, the incidence of PONV was lower after premedication with oral tropisetron than after ondansetron or metoclopramide. Considering the entire 24-h postoperative period, the incidence of PONV was the same after all three premedications, but the incidence of vomiting was lower after oral ondansetron and tropisetron than after metoclopramide.

Selective spinal anesthesia: a comparison of hyperbaric bupivacaine 4 mg versus 6 mg for outpatient knee arthroscopy.

IMPLICATIONS: A low-dose (4 mg), low-volume (0.8 mL), low-flow (2 min) technique with hyperbaric bupivacaine toward the dependent side oriented injection and maintenance of the lateral decubitus position for 10 min produced selective spinal anesthesia with rapid recession of motor block and early discharge home.

Chiral HPLC separation and CD spectra of the enantiomers of the alkaloid tacamonine and related compounds.

The HPLC enantiomeric separation of racemic indole alkaloids tacamonine, 17 alpha-hydroxytacamonine, deethyleburnamonine, and vindeburnol was accomplished using Chiralpak AD and Chiralcel OD as chiral stationary phases. Small structural differences affect the enantioselectivity ability of these phases. Single enantiomers of tacamonine and vindeburnol were isolated by semipreparative HPLC and their CD spectra and optical rotations were measured.

Postoperative nausea and vomiting after sevoflurane with or without ondansetron compared with propofol in female patients undergoing breast surgery.

IMPLICATIONS: We studied 180 female patients undergoing breast surgery. The patients were randomly allocated to receive one of three anesthetic techniques. Compared with either propofol or sevoflurane alone, sevoflurane with ondansetron resulted in a decreased incidence of postoperative nausea and vomiting. Sevoflurane with ondansetron prophylaxis is a good alternative to propofol with respect to avoiding postoperative nausea and vomiting.

Effect of stable fish oil on arterial thrombogenesis, platelet aggregation, and superoxide dismutase activity.

We examined the influence of dietary stable fish oil on aortic thrombosis, platelet aggregation, and superoxide dismutase (SOD) activity in a rat model. Twenty-nine Sprague-Dawley rats were fed regular chow supplemented with stable fish oil preparation (for 1 or 3 weeks), and 37 rats fed regular chow served as controls. The abdominal cavity was opened, and the abdominal aorta isolated. Whatman paper impregnated with 35% FeCl3 was wrapped around the surface of the aorta, and aortic flow was continuously recorded. In control rats, an occlusive platelet-fibrin-rich thrombus was formed in 21 +/- 3 min. Dietary fish oil in a time-dependent fashion delayed time to thrombus formation (24 +/- 2 min in rats fed fish oil for 1 week and 31 +/- 2 min in rats fed fish oil for 3 weeks), inhibited platelet aggregation (21 +/- 5% vs. 45 +/- 6%; p < 0.01) and increased SOD activity (p < 0.01). We conclude that dietary supplementation with stable fish oil delays formation of arterial thrombus, probably by reducing platelet aggregation and oxidative stress-associated arterial injury.

Comparison of ondansetron and tropisetron combined with droperidol for the prevention of emesis in women with a history of post-operative nausea and vomiting.

The anti-emetic efficacy of prophylactic ondansetron and tropisetron in combination with a low dose of droperidol in patients with high probability for post-operative nausea and vomiting undergoing gynaecological laparoscopy was compared. Patients were randomly allocated in a double-blind manner to receive either ondansetron 8 mg (n = 45) or tropisetron 5 mg (n = 43) at the end of surgery. A standardized general anaesthetic technique was used, including droperidol 0.75 mg. The incidence of nausea was 36% and 49% (P = 0.28), and vomiting occurred in 13% and 14% of the patients in the ondansetron and tropisetron groups, respectively. The onset time for rescue medication was significantly sooner after tropisetron than ondansetron (3 h 18 min vs. 6 h 25 min; P = 0.007). There were no statistically significant differences in efficacy between prophylactic ondansetron and tropisetron combined with droperidol in a high-risk population. However, ondansetron appeared to be more effective in preventing post-operative nausea and vomiting in the early hours after surgery compared with tropisetron.

Tropisetron or droperidol in the prevention of postoperative nausea and vomiting. A comparative, randomised, double-blind study in women undergoing laparoscopic cholecystectomy.

BACKGROUND: Women undergoing laparoscopic cholecystectomy are susceptible to postoperative nausea and vomiting (PONV). This study was undertaken to evaluate the efficacy of tropisetron or droperidol for preventing PONV after laparoscopic cholecystectomy. METHODS: In a prospective, randomised, double-blind trial, 120 female patients received either tropisetron 5 mg or droperidol 1.25 mg intravenously at the beginning of surgery. A standard general anaesthetic technique and postoperative analgesia were used. Nausea, emetic episodes and the need for rescue medication were recorded for 24 h postoperatively. RESULTS: Nausea was experienced by 55% of the patients in the tropisetron group and by 62% in the droperidol group (ns). The incidence of emetic episodes was 20% and 52% (P=0.001) in the two groups, respectively. Rescue antiemetic medication was needed in 42% and 50% (ns) of the patients, respectively. Patients in the droperidol group were more drowsy in comparison with patients in the tropisetron group, mean sedation score being 6.7 vs 5.7, respectively (P=0.023). No difference in other side-effects was observed. CONCLUSION: Tropisetron, when compared with droperidol, had no better efficacy on the prevention of postoperative nausea but resulted in a significantly lower incidence of vomiting after laparoscopic cholecystectomy.