Prophylaxis of intra- and postoperative nausea and vomiting in patients during cesarean section in spinal anesthesia.

BACKGROUND: This paper describes a randomized prospective study conducted in 308 patients undergoing caesarean section in spinal anaesthesia at a single hospital between 2010 and 2012 to find a suitable anti-emetic strategy for these patients. MATERIAL AND METHODS: Spinal anesthesia was performed in left prone position, at L3/L4 with hyperbaric 0.5% Bupivacaine according to a cc/cm body height ratio. There were no opioids given peri-operatively. The patients received either no prophylaxis (Group I) or tropisetron and metoclopramide (Group II) or dimenhydrinate and dexamethasone (Group III), or tropisetron as a single medication (Group IV). The primary outcome was nausea and/or vomiting (NV) in the intraoperative, early (0-2 h) or late (2-24 h) postoperative period. Multivariate statistical analysis was conducted with a regression analysis and a backward elimination of factors without significant correlation. RESULTS: All prophylactic agents significantly reduced NV incidence intraoperatively. Relative risk reduction for NV by prophylaxis was most effective (59.5%) in Group II (tropisetron and metoclopramide). In Group III (dimenhydrinate and dexamethasone), NV risk was reduced by 29.9% and by 28.7% in Group IV (tropisetron mono-therapy). The incidence of NV in the early (0?2 h) and the late (2?24 h) postoperative period was low all over (7.8%), but the relative risk reduction of NV in the early postoperative period was 54.1% (Group IV), 45.1% (Group III), and 34.8% (Group II), respectively. In the late postoperative period, there was no significant difference between the 4 groups. CONCLUSIONS: We recommend a prophylactic medication with tropisetron 2 mg and metoclopramide 20 mg for patients during caesarean section. These agents are safe, reasonably priced, and highly efficient in preventing nausea and vomiting.

Microvascular changes following four-hour single arteriole occlusion.

BACKGROUND: Free tissue transplantations are lengthy procedures that result in prolong tissue ischemia. Restoral of blood flow is essential for free flap recovery; however, upon reperfusion tissue that is viable may continue to be nonperfused. To further elucidate this pathophysiology skeletal muscle microcirculation was investigated during reperfusion following 4-hour single arteriole occlusion. MATERIALS AND METHODS: A blunt micropipette probe was use to compress a single arteriole in the unanesthetized hamster (N = 20) dorsal skinfold chamber. Arteriole (n = 20), capillary (n = 97), and postcapillary venule (n = 16) diameters and blood flow were analyzed at 0, 30, 60, 120, 240 min and 24 hours of reperfusion after 4 hour occlusion. RESULTS: Feeding arcade arterioles exhibited a brief (<10 min) vasoconstriction [0.31 ± 0.26 (mean ± SE) of baseline] upon reperfusion followed by a maximum vasodilation at 120 min (1.3 ± 0.10: P < 0.05). Vasodilation was observed in transverse arterioles (A3) (1.8 ± 0.20: P < 0.05). Correspondingly, all arteriole and venule flow was increased by 120 min (P < 0.05) of reperfusion. There was a transient decrease in the number of flowing capillaries at 0 and 30 min reperfusion (0.73 ± 0.09 and 0.84 ± 0.06: P < 0.05, respectively). CONCLUSIONS: At the onset of reperfusion heterogeneous arteriole flow and transient decrease in flowing capillaries was observed; however, return of flow in all capillaries and an eventual hyperemic response in all arterioles suggests the reversible nature of this response. Single arteriole occlusion may allow for a more controlled and detailed microcirculatory analysis during ischemia-reperfusion.

Prophylaxis of postoperative nausea and vomiting in elective breast surgery.

STUDY OBJECTIVE: To evaluate strategies to treat postoperative nausea and vomiting (PONV) in patients undergoing elective breast surgery. DESIGN: Prospective, randomized, double-blinded, placebo-controlled trial. SETTING: University-affiliated hospital. PATIENTS: 480 patients with risk factors for PONV. INTERVENTIONS: Patients were randomized to three groups to receive an antiemetic prophylactic combination of haloperidol and tropisetron (Group HT), dimenhydrinate and dexamethasone (Group DD), or no prophylaxis (Group P). Anesthesia was maintained with volatile anesthesia (desflurane or sevoflurane) and fentanyl or total intravenous anesthesia (TIVA). MEASUREMENTS: Incidence of nausea, emesis, or both in the early (0 - 2 hrs) and late (2 - 24 hrs) postoperative periods were recorded, as were the number of episodes and the time of each occurrence; and patient assessment of the PONV experience on a scale comparable to a numeric rating scale (NRS). MAIN RESULTS: Both antiemetic combinations significantly reduced PONV incidence. In patients who received no prophylaxis, PONV incidence was 48.2% in patients given volatile anesthetics and 43.8% in those who received TIVA. PONV incidence was 17.5% in the Group HT patients who received volatile anesthetics, and 25% in the Group HT patients who received TIVA. PONV incidence was 11.4% in Group DD patients given volatile anesthetics, and 15% in Group DD patients receiving TIVA. TIVA reduced the incidence of PONV in the early postoperative period (0-2 hrs), but increased PONV incidence in the late period (2-24 hrs). Patients given TIVA with propofol and remifentanil intraoperatively required more opioids postoperatively than patients given volatile anesthetics. CONCLUSION: The frequency of PONV was reduced significantly with both antiemetic combinations.

Excessive erythrocytosis does not elevate capillary oxygen delivery in subcutaneous mouse tissue.

OBJECTIVE: Acclimatization to reduced environmental oxygen includes erythropoietin-regulated increase in erythrocytes enhancing the blood's oxygen content. However, increased hematocrit levels result in elevated blood viscosity that might impair microcirculation and tissue oxygenation. To assess this oxygen supply to the skin, the authors used erythropoietin overexpressing transgenic mice (tg6) that develop excessive erythrocytosis in an oxygen-independent manner. These animals have been previously reported to elevate their blood viscosity 4-fold. METHODS: The partial oxygen pressure (pO2) distribution was evaluated in microvessels as well as in subcutaneous interstitial tissue within a dorsal skinfold chamber of resting conscious mice using automated phosphorescence quenching. RESULTS: Compared to wildtype (wt) animals, transgenic blood viscosity increased 4-fold but microvessel diameter was not altered. Despite sharing similar blood pO2 as the wt siblings, tg6 animals nearly doubled their oxygen content. Moreover, tg6 erythrocytes reduced hemoglobin's oxygen affinity by decreased 2,3-DPG levels and an increased Hill number. Transgenic arterioles and venules showed increased pO2 compared to wt controls whereas capillary and tissue pO2 were not altered. CONCLUSIONS: Excessive erythrocytosis does not elevate capillary oxygen delivery.

Excessive methaemoglobinaemia and multi-organ failure following 4-DMAP antidote therapy.

This report describes the clinical history of a patient intoxicated with methyl isocyanate (MIC), a toxic agent first receiving attention in 1984 after a mass accident in a pesticide plant in Bhopal, India, and treated with the cyanide-specific antidote 4-DMAP. The numerous clinical conditions requiring 39-day intensive care treatment included ARDS, renal and hepatic failure, haemolysis, bone marrow depression, septic encephalopathy and critical illness polyneuropathy. The most outstanding condition, however, was a methaemoglobinemia of 86.7%, which was predominantly related to the use of 4-DMAP, although uptake of MIC may have been a significant contributing factor. Since significant cyanide intoxication could be excluded clinically and by laboratory testing in the initial phase of emergency treatment, most of the clinical effects were due to the side-effects of the antidote therapy. Due to intensive therapy, the patient survived without any neurological or organ deficit. This case shows that antidotes should be used cautiously in cases where uncertainties about the nature of the underlying toxic agent exist. This may prevent severe side-effects associated with antidote therapy, e.g. 4-DMAP, if there is-as in our case-a mismatch between the toxic agent and the antidote.

A factorial trial of six interventions for the prevention of postoperative nausea and vomiting.

BACKGROUND: Untreated, one third of patients who undergo surgery will have postoperative nausea and vomiting. Although many trials have been conducted, the relative benefits of prophylactic antiemetic interventions given alone or in combination remain unknown. METHODS: We enrolled 5199 patients at high risk for postoperative nausea and vomiting in a randomized, controlled trial of factorial design that was powered to evaluate interactions among as many as three antiemetic interventions. Of these patients, 4123 were randomly assigned to 1 of 64 possible combinations of six prophylactic interventions: 4 mg of ondansetron or no ondansetron; 4 mg of dexamethasone or no dexamethasone; 1.25 mg of droperidol or no droperidol; propofol or a volatile anesthetic; nitrogen or nitrous oxide; and remifentanil or fentanyl. The remaining patients were randomly assigned with respect to the first four interventions. The primary outcome was nausea and vomiting within 24 hours after surgery, which was evaluated blindly. RESULTS: Ondansetron, dexamethasone, and droperidol each reduced the risk of postoperative nausea and vomiting by about 26 percent. Propofol reduced the risk by 19 percent, and nitrogen by 12 percent; the risk reduction with both of these agents (i.e., total intravenous anesthesia) was thus similar to that observed with each of the antiemetics. All the interventions acted independently of one another and independently of the patients' baseline risk. Consequently, the relative risks associated with the combined interventions could be estimated by multiplying the relative risks associated with each intervention. Absolute risk reduction, though, was a critical function of patients' baseline risk. CONCLUSIONS: Because antiemetic interventions are similarly effective and act independently, the safest or least expensive should be used first. Prophylaxis is rarely warranted in low-risk patients, moderate-risk patients may benefit from a single intervention, and multiple interventions should be reserved for high-risk patients.

Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms.

Destruction of existing tumor blood vessels may be achieved by targeting vascular endothelial growth factor (VEGF) signaling, which mediates not only endothelial cell proliferation but also endothelial cell survival. In this study, however, intravital microscopy failed to demonstrate that targeting of VEGFR-2 (by the tyrosine kinase inhibitor SU5416) induces significant regression of experimental tumor blood vessels. Immunohistochemistry, electron microscopy, expression analyses, and in situ hybridization provide evidence that this resistance of tumor blood vessels to VEGFR-2 targeting is conferred by pericytes that stabilize blood vessels and provide endothelial cell survival signals via the Ang-1/Tie2 pathway. In contrast, targeting VEGFR-2 plus the platelet-derived growth factor receptor (PDGFR)-beta system (PDGFR-beta) signaling (by SU6668) rapidly forced 40% of tumor blood vessels into regression, rendering these tumors hypoxic as shown by phosphorescence quenching. TUNEL staining, electron microscopy, and apoptosis blocking experiments suggest that VEGFR-2 plus PDGFR-beta targeting enforced tumor blood vessel regression by inducing endothelial cell apoptosis. We further show that this is achieved by an interference with pericyte-endothelial cell interaction. This study provides novel insights into the mechanisms of how 1) pericytes may provide escape strategies to anti-angiogenic therapies and 2) novel concepts that target not only endothelial cells but also pericyte-associated pathways involved in vascular stabilization and maturation exert potent anti-vascular effects.

Gas gangrene pyaemia with myocardial abscess formation--fatal outcome from a rare infection nowadays.

We report a case of sudden death after gas gangrene. A 67-year-old male patient with diabetes mellitus and chronic renal failure (on haemodialysis three times a week) presented in the surgical emergency department with a severe swelling and crepitation in the right groin. No signs of trauma were present-except for a well-healed, 1-year-old scar after femoro-popliteal bypass surgery. Two days earlier, he had presented to the internal medicine department with epigastric pain and had left against medical advice. On readmission the patient was initially conscious and in a stable cardiopulmonary condition but developed sudden cardiocirculatory failure and underwent resuscitation. Despite all resuscitation measures, including the administration of high doses of catecholamines and the treatment of hyperkalemia, the patient died. Autopsy revealed septicaemia with rod-shaped gram-positive bacteria, typical of Clostridium perfringens, evidenced by multiple areas of myonecrosis. Abscess formation was found in the myocardium. Clostridial gas gangrene is a rare clinical condition. Unless immediate diagnosis and adequate therapy measures are taken, the outcome and chances for survival are poor as demonstrated by this case.

pO(2) measurements by phosphorescence quenching: characteristics and applications of an automated system.

An automated system for pO(2) analysis based upon phosphorescence quenching was tested. The system was calibrated in vitro with capillary samples of saline and blood. Results were compared to a conventional measuring procedure wherein pO(2) was calculated off-line by computer fitting of phosphorescence decay signals. PO(2) measurements obtained by the automated system were correlated (r(2) = 0.98) with readings simultaneously generated by a blood gas analyzer, accuracy being highest in the low (0-20 mm Hg) and medium pO(2) ranges (21-70 mm Hg). Measurements in in vivo studies in the hamster skin-fold preparation were similar to previously reported results. The automated system fits the phosphorescence decay data to a single exponential and allows repeated pO(2) measurements in rapid sequence.