Postoperative nausea and vomiting after unrestricted clear fluids before day surgery: A retrospective analysis.

BACKGROUND: Guidance on pre-operative fluids fasting policy continues to evolve. Current European guidelines encourage the intake of oral fluids up to 2 h before the induction of general anaesthesia. From October 2014, Torbay Hospital Day Surgery Unit commenced an unrestricted fluid policy, encouraging patients to drink clear fluids up until the time of transfer to theatre. OBJECTIVE: The aim of this study was to assess the incidence of postoperative nausea and vomiting before and after the change to the unrestricted pre-operative clear oral fluids. DESIGN: Retrospective, before and after study. SETTING: Single district general hospital between November 2013 and February 2016. PATIENTS: A total of 11 500 patients on the day case pathway who were receiving either sedation, general anaesthesia, regional anaesthesia or their combination. The data from these patients were collected routinely. This number of patients represents approximately 78% of all patients before the change in fluids policy and 74% after the change. Exclusions were patients undergoing a termination of pregnancy, or patients undergoing community dental procedures, from whom patient experience data are not collected. INTERVENTION: Introduction of a change to the day surgery pathway policy permitting unrestricted clear oral fluids preoperatively until transfer to theatre (from October 2014). MAIN OUTCOME MEASURES: Incidence of postoperative nausea and vomiting. RESULTS: The rates of nausea within 24 h postoperatively were 270/5192 (5.2%) when patients could not drink within 2 h of surgery, and 179/4724 (3.8%) when patients could drink up until surgery, a relative rate (95% confidence interval) of 0.73 (0.61 to 0.88), P = 0.00074. The corresponding rates of vomiting were 146/5186 (2.8%) and 104/4716 (2.2%), a relative rate (95% confidence interval) of 0.78 (0.61 to 1.00), P = 0.053. CONCLUSION: Our data suggest that the liberal consumption of clear fluids before the induction of scheduled day case anaesthesia reduced the rates of postoperative nausea and vomiting.

Gene expression subtypes in patients with chronic fatigue syndrome/myalgic encephalomyelitis.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem disease, the pathogenesis of which remains undetermined. We set out to determine the precise abnormalities of gene expression in the blood of patients with CFS/ME. We analyzed gene expression in peripheral blood from 25 patients with CFS/ME diagnosed according to the Centers for Disease Control and Prevention diagnostic criteria and 50 healthy blood donors, using a microarray with a cutoff fold difference of expression of >or=2.5. Genes showing differential expression were further analyzed in 55 patients with CFS/ME and 75 healthy blood donors, using quantitative polymerase chain reaction. Differential expression was confirmed for 88 genes; 85 were upregulated, and 3 were downregulated. Highly represented functions were hematological disease and function, immunological disease and function, cancer, cell death, immune response, and infection. Clustering of quantitative polymerase chain reaction data from patients with CFS/ME revealed 7 subtypes with distinct differences in Medical Outcomes Survey Short Form-36 scores, clinical phenotypes, and severity.

Comparison of two rat models of cerebral ischemia under hyperglycemic conditions.

Hyperglycemia worsens outcome of stroke either in the clinical setting or in animal models. In the present study, two focal cerebral ischemia models, permanent middle cerebral artery occlusion (MCAO, 3-4 h) and reversible MCAO (1 h ischemia + 3 h reperfusion), under hyperglycemic conditions were compared. Using 2,3,5-triphenyltetrazolium chloride staining to define viable tissue, this resulted in the infarction area being confined primarily to the cerebral cortex in the permanent MCAO group, while it extended to the subcortical area in the reversible MCAO group, and the lesion areas were respectively 27.7 +/- 5.3% and 46.8 +/- 12.0% of the ipsilateral hemisphere (P = 0.012). Hyperglycemia accelerated the cerebral damage compared to normoglycemia and ascorbic acid pre-treatment maintained tissue viability during the acute phase of hyperglycemic MCAO. In conclusion, hyperglycemia combined with either of the two MCAO models resulted in rapid infarction associated with increased oxidative stress. The hyperglycemic models are suitable for pharmaceutical therapeutic studies of antioxidant efficacy.

Increased oxidative stress during hyperglycemic cerebral ischemia.

In this review, we summarize the role of hyperglycemia during cerebral ischemia. Hyperglycemia occurring during experimental and clinical stroke has been associated with increased cerebral damage. Increased oxidative stress resulting from hyperglycemia is believed to contribute to the exacerbated damage. More specifically, superoxide, nitric oxide and peroxynitrite are believed to play an important role in cerebral damage. This also involves increased recruitment of various blood cells to the ischemic zone that contribute to inflammation. We present data from our group and others that demonstrate that free radical production is increased during hyperglycemic stroke in rodents. Recent data suggest that inflammation is an important component of ischemic damage under both normo- and hyperglycemic conditions. We summarize numerous studies that indicate that a variety of antioxidant (inhibition of free radical production, scavenging of free radicals and increasing free radical degradation) and anti-inflammatory strategies decrease cerebral infarction. Finally, we compare the success of some of these strategies in clinical trials compared to the animal models.

Establishment of an operating room committee and a training program to improve aseptic techniques for rodent and large animal surgery.

Investigators of our research facility generally accept the concept of asepsis as an important component of adequate surgical care for animals. However, they experience difficulties putting it into practice, especially in the case of rodents. The reasons for this are inconvenience, cost, and lack of training. To better assist investigators in the implementation of aseptic surgical techniques in their laboratories, we have created an Operating Room (OR) Committee modeled after OR committees found in human hospitals. A reconstructive surgeon, a veterinarian, a research scientist, a nurse involved in the training of OR personnel, interns, graduate students, and an animal health technician were chosen as committee members in light of their OR and animal care expertise. The first task of the OR Committee was to establish institutional guidelines for aseptic surgery, taking into account the costs imposed on research budgets by these procedures. The OR Committee also supports a complete training program in aseptic surgery techniques, which consists of lectures, a training manual, videos, and a practical course. Furthermore, when experimental procedures require specialized equipment, the OR Committee collaborates with researchers to develop strategies to achieve asepsis. This OR Committee and the training program proved to be important tools to promote and improve the quality of animal care during surgery.

Dehydroascorbic acid normalizes several markers of oxidative stress and inflammation in acute hyperglycemic focal cerebral ischemia in the rat.

We investigated the effect of dehydroascorbic acid (DHA), the oxidized form of vitamin C which is a superoxide scavenger, on manganese superoxide dismutase (MnSOD), copper-zinc SOD (CuZnSOD), cyclooxygenase-2 (COX-2) and interleukin-1beta (IL-1beta) expression in a rat model of focal cerebral ischemia under normo- and hyperglycemic conditions. Edema formation was also assessed. MnSOD, CuZnSOD, COX-2 and IL-1beta mRNA and protein expression were studied 3 h post-ischemia. No changes were observed in MnSOD and CuZnSOD mRNA expression among the groups. COX-2 and IL-1beta mRNA expression were upregulated by ischemia but were not influenced by the glycemic state. At the protein level, hyperglycemic cerebral ischemia increased MnSOD and CuZnSOD [Bémeur, C., Ste-Marie, L., Desjardins, P., Butterworth, R.F., Vachon, L., Montgomery, J., Hazell, A.S., 2004a. Expression of superoxide dismutase in hyperglycemic focal cerebral ischemia in the rat. Neurochem. Int. 45, 1167-1174] and IL-1beta expression compared to normoglycemic ischemia. COX-2 protein expression was also significantly higher following hyperglycemic ischemia compared to hyperglycemic shams. DHA administration did not change the pattern of COX-2 or IL-1beta mRNA expression, but normalized the increased protein expression following hyperglycemic ischemia. DHA administration also normalized MnSOD and CuZnSOD protein expression to the levels observed in normoglycemic ischemic animals. Edema formation was significantly reduced by DHA administration in hyperglycemic ischemic animals. The DHA-induced post-transcriptional normalization of MnSOD, CuZnSOD, COX-2 and IL-1beta levels and the decreased edema formation suggest that hyperglycemia accelerates superoxide formation and the inflammatory response, thus contributing to early damage in hyperglycemic stroke and strategies to scavenge superoxide should be an important therapeutic avenue.

Expression of superoxide dismutase in hyperglycemic focal cerebral ischemia in the rat.

This study investigated the possibility that hyperglycemia induces early expression of various superoxide dismutases (SOD) and nitric oxide synthases (NOS) following focal cerebral ischemia in the rat. MnSOD, CuZnSOD, nNOS and eNOS mRNA and protein expression were examined 3 h after permanent middle cerebral artery occlusion under acute hyperglycemic or normoglycemic conditions. 2,3,5-triphenyltetrazolium chloride (TTC) treatment post-mortem revealed a significant area at risk of infarction following ischemia in hyperglycemic compared to normoglycemic rats. Although no changes in MnSOD, CuZnSOD, nNOS and eNOS mRNA expression were detected, Western blots of ischemic cortex revealed an increase in MnSOD and CuZnSOD protein expression in hyperglycemic compared to normoglycemic rats. Pre-treatment of hyperglycemic rats with the NOS inhibitors L-nitroarginine methyl ester (L-NAME) and 7-nitroindazole (7-NI) or dehydroascorbic acid (DHA), a superoxide scavenger, significantly reduced the TTC delineated zone. The hyperglycemia-induced post-transcriptional upregulation of MnSOD and CuZnSOD levels suggest a response to increased superoxide production which, in the presence of increased nitric oxide production, may play a major role in the increased risk of damage following hyperglycemic stroke.

Increased brain serotonin turnover correlates with the degree of shunting and hyperammonemia in rats following variable portal vein stenosis.

BACKGROUND/AIMS: Hepatic encephalopathy (HE) is a serious neuropsychiatric complication of chronic liver disease. Brain monoamines have been implicated in the pathogenesis of HE. We examined the relationship between monoamine dysfunction and the degree of portal-systemic shunting (PSS) in rats with varying degrees of PSS. METHODS: Concentrations of catecholamines, serotonin, histamine, precursors and metabolites in frontal cortex of rats with varying degrees of PSS (9-99.8%) were measured by HPLC. RESULTS: The concentrations of the serotonin precursor, tryptophan, and its metabolite, 5-HIAA were increased up to 4-fold in brains of rats with various degrees of PSS and were significantly correlated with the degree of shunting and with arterial ammonia levels. Brain levels of histamine, its precursor, l-histidine, and metabolite, tele-methylhistamine were significantly increased only following total shunting. Concentrations of catecholamines and their metabolites were not significantly correlated with degree of PSS or hyperammonemia. CONCLUSIONS: Given the established role of the serotonin system in the regulation of sleep, circadian rhythmicity and locomotion these findings suggest that selective alterations of this system could be implicated in the pathogenesis of HE. Therapeutic approaches aimed at the normalization of serotonin turnover could be beneficial in the prevention and treatment of early neuropsychiatric symptoms of HE.

Decreased beta-actin mRNA expression in hyperglycemic focal cerebral ischemia in the rat.

beta-Actin is often used as a housekeeping gene when performing reverse transcription-polymerase chain reaction (RT-PCR) analysis for cerebral ischemia models. In the present study, we tested two different control genes used for RT-PCR experiments, beta-actin and porphobilinogen deaminase (PBG-D), in a rat model of focal cerebral ischemia under normo- or hyperglycemic conditions. A three-vessel occlusion model with permanent middle cerebral artery occlusion was used in the rat. beta-Actin mRNA expression was decreased in hyperglycemic ischemic rats compared to normoglycemic ischemic animals 3 h post-ischemia. beta-Actin protein content was unchanged. As for PBG-D, its mRNA expression remained constant throughout the groups. Our data thus show that, following focal cerebral ischemia in hyperglycemic conditions, beta-actin is an unsuitable housekeeping gene whereas PBG-D is more appropriate. This study clearly demonstrates the importance of selecting a stable housekeeping gene when performing RT-PCR experiments.

Pitx3 is required for motor activity and for survival of a subset of midbrain dopaminergic neurons.

Mesencephalic dopaminergic (MesDA) neurons play crucial roles in motor and behavioral processes; their loss in Parkinson's disease (PD) results in striatal dopamine (DA) deficiency and hypokinetic movement disorder. The Pitx3 homeobox gene is expressed in the MesDA system. We now show that only a subset of MesDA neurons express Pitx3 and that in Pitx3-deficient aphakia mice, this subset is progressively lost by apoptosis during fetal (substantia nigra, SN) and postnatal (ventral tegmental area) development, resulting in very low striatal DA and akinesia. Similar to human PD, dorsal SN neurons (which are Pitx3 negative) are spared in mutant mice. Thus, Pitx3 defines a pathway for survival of neurons that are implicated in PD and that are required for spontaneous locomotor activity.

Cyclosporin A in blood and brain tissue following intra-carotid injections in normal and stroke-induced rats.

Administration of Cyclosporin A (CsA) to rats undergoing reversible global or focal ischemia has been demonstrated to be variably neuroprotective. As CsA does not readily cross the blood-brain barrier, the variability may be due to differences in bioavailability of CsA to the ischemic brain. We have, therefore, quantitated CsA levels in blood and brain following intra-carotid injection in rats undergoing permanent right middle cerebral artery (MCA) occlusion using a three-vessel model of focal cerebral ischemia. After 30 min of three-vessel occlusion, CsA (10 mg/kg) was injected into the left external carotid artery followed by reversal of the left common carotid artery occlusion. At various times post-injection, blood samples were collected from the vena cava and samples of ischemic or sham-operated cortex were obtained for CsA quantitation by tandem mass spectrometry. Pharmacokinetic parameters were determined using non-linear mixed-effects modeling. CsA areas under the curve between normal and stroke-induced rats were not significantly different in blood (18355 vs. 19405 ng x h/ml, NS) or in brain tissue (15664 vs. 14931 ng x h/g, NS). These results demonstrate that intra-carotid injection of CsA results in high levels in brain (brain-blood ratio from 0.5 to 1). No significant differences in blood and brain exposure were observed between normal and stroke-induced rats. Therefore, reduced cerebral blood flow in the ischemic territory did not limit CsA availability to the cortex. In addition, CsA intra-carotid administration was neuroprotective following 24 h recovery as there was a significant decrease in the infarct area of the affected hemisphere compared to saline injected rats as estimated by TTC staining of viable tissue.