Leo van Wolfswinkel

Incidence of intraoperative hypotension as a function of the chosen definition: literature definitions applied to a retrospective cohort using automated data collection.

Background: Intraoperative hypotension (IOH) is a common side effect of general anesthesia and has been reported to be associated with adverse perioperative outcomes. These associations were found using different definitions for IOH. It is unknown whether the incidences of IOH found with those different definitions are comparable. The authors aimed to describe the relation between the chosen definition and incidence of IOH. Methods: First, a systematic literature search was performed to identify recent definitions of IOH that have been used in the anesthesia literature. Subsequently, these definitions were applied to a cohort of 15,509 consecutive adult patients undergoing noncardiac surgery during general anesthesia. The incidence of IOH according to the different threshold values was calculated, and the effect of a defined minimal duration of a hypotensive episode was studied. Results: Many different definitions of IOH were found. When applied to a cohort of patients, these different definitions resulted in different IOH incidences. Any episode of systolic blood pressure below 80 mmHg was found in 41% of the patients, whereas 93% of the patients had at least one episode of systolic blood pressure more than 20% below baseline. Both definitions are frequently used in the literature. The relation between threshold values from the literature and IOH incidence shows an S-shaped cumulative incidence curve, with occurrence frequencies of IOH varying from 5% to 99%. Conclusions: There is no widely accepted definition of IOH. With varying definitions, many different incidences can be reproduced. This might have implications for previously described associations between IOH and adverse outcomes.

Intraoperative Hypotension and 1-Year Mortality after Noncardiac Surgery

Background:Intraoperative hypotension (IOH) is frequently associated with adverse outcome such as 1-yr mortality. However, there is no consensus on the correct definition of IOH. The authors studied a number of different definitions of IOH, based on blood pressure thresholds and minimal episode durations, and their association with 1-yr mortality after noncardiac surgery. Methods:This cohort study included 1,705 consecutive adult patients who underwent general and vascular surgery. Data on IOH and potentially confounding variables were obtained from electronic record-keeping systems. Mortality data were collected up to 1 yr after surgery. The authors used two different techniques to reduce the influence of confounding variables, multivariable Cox proportional hazard regression modeling and classification and regression tree analysis. Results:The mortality within 1 yr after surgery was 5.2% (88 patients). After adjustment for confounding, the Cox regression analysis did not show an association between IOH and the risk of dying within 1 yr after surgery (hazard ratio around 1.00 with high P values for different definitions of IOH). Additional classification and regression tree analysis identified IOH as a predictor for 1-yr mortality in elderly patients. When the blood pressure threshold for IOH was decreased, the duration of IOH at which this association was found was decreased as well. Conclusions:This observational study showed no causal relation between IOH and 1-yr mortality after noncardiac surgery for any of the definitions of IOH. Nevertheless, additional analysis suggested that for elderly patients, the mortality risk increases when the duration of IOH becomes long enough. The length of this duration depends on the designated blood pressure threshold, suggesting that lower blood pressures are tolerated for shorter durations. The effect of IOH on 1-yr mortality remains debatable, and no firm conclusions on the lowest acceptable intraoperative blood pressures can be drawn from this study.

Endogenous opioids and reward.

The discovery of endogenous opioids has markedly influenced the research on the biology of addiction and reward brain processes. Evidence has been presented that these brain substances modulate brain stimulation reward, self-administration of different drugs of abuse, sexual behaviour and social behaviour. There appears to be two different domains in which endogenous opioids, present in separate and distinct brain regions, are involved. One is related to the modulation of incentive motivational processes and the other to the performance of certain behaviours. It is concluded that endogenous opioids may play a role in the vulnerability to certain diseases, such as addiction and autism, but also when the disease is present, such as alcoholism.

Association between intraoperative hypotension and myocardial injury after vascular surgery

Background:Postoperative myocardial injury occurs frequently after noncardiac surgery and is strongly associated with mortality. Intraoperative hypotension (IOH) is hypothesized to be a possible cause. The aim of this study was to determine the association between IOH and postoperative myocardial injury. Methods:This cohort study included 890 consecutive patients aged 60 yr or older undergoing vascular surgery from two university centers. The occurrence of myocardial injury was assessed by troponin measurements as part of a postoperative care protocol. IOH was defined by four different thresholds using either relative or absolute values of the mean arterial blood pressure based on previous studies. Either invasive or noninvasive blood pressure measurements were used. Poisson regression analysis was used to determine the association between IOH and postoperative myocardial injury, adjusted for potential clinical confounders and multiple comparisons. Results:Depending on the definition used, IOH occurred in 12 to 81% of the patients. Postoperative myocardial injury occurred in 131 (29%) patients with IOH as defined by a mean arterial pressure less than 60 mmHg, compared with 87 (20%) patients without IOH (P = 0.001). After adjustment for potential confounding factors including mean heart rates, a 40% decrease from the preinduction mean arterial blood pressure with a cumulative duration of more than 30 min was associated with postoperative myocardial injury (relative risk, 1.8; 99% CI, 1.2 to 2.6, P < 0.001). Shorter cumulative durations (less than 30 min) were not associated with myocardial injury. Postoperative myocardial infarction and death within 30 days occurred in 26 (6%) and 17 (4%) patients with IOH as defined by a mean arterial pressure less than 60 mmHg, compared with 12 (3%; P = 0.08) and 15 (3%; P = 0.77) patients without IOH, respectively. Conclusions:In elderly vascular surgery patients, IOH defined as a 40% decrease from the preinduction mean arterial blood pressure with a cumulative duration of more than 30 min was associated with postoperative myocardial injury.

Impact of risk assessments on prophylactic antiemetic prescription and the incidence of postoperative nausea and vomiting: a cluster-randomized trial.

Background:Clinical prediction models have been shown to have moderate sensitivity and specificity, yet their use will depend on implementation in clinical practice. The authors hypothesized that implementation of a prediction model for postoperative nausea and vomiting (PONV) would lower the PONV incidence by stimulating anesthesiologists to administer more “risk-tailored” prophylaxis to patients. Methods:A single-center, cluster-randomized trial was performed in 12,032 elective surgical patients receiving anesthesia from 79 anesthesiologists. Anesthesiologists were randomized to either exposure or nonexposure to automated risk calculations for PONV (without patient-specific recommendations on prophylactic antiemetics). Anesthesiologists who treated less than 50 enrolled patients were excluded during the analysis to avoid too small clusters, yielding 11,613 patients and 57 anesthesiologists (intervention group: 5,471 and 31; care-as-usual group: 6,142 and 26). The 24-h incidence of PONV (primary outcome) and the number of prophylactic antiemetics administered per patient were studied for risk-dependent differences between allocation groups. Results:There were no differences in PONV incidence between allocation groups (crude incidence intervention group 41%, care-as-usual group 43%; odds ratio, 0.97; 95% CI, 0.87–1.1; risk-dependent odds ratio, 0.92; 95% CI, 0.80–1.1). Nevertheless, intervention-group anesthesiologists administered more prophylactic antiemetics (rate ratio, 2.0; 95% CI, 1.6–2.4) and more risk-tailored than care-as-usual–group anesthesiologists (risk-dependent rate ratio, 1.6; 95% CI, 1.3–2.0). Conclusions:Implementation of a PONV prediction model did not reduce the PONV incidence despite increased antiemetic prescription in high-risk patients by anesthesiologists. Before implementing prediction models into clinical practice, implementation studies that include patient outcomes as an endpoint are needed.

Incidence of intraoperative hypoxemia in children in relation to age.

BACKGROUND:Although respiratory problems are by far the most frequent complications of pediatric anesthesia, there are currently no reliable data on the incidence of perioperative hypoxemia in children. Most studies investigating the incidence of pediatric respiratory complications were based on self-report. METHODS:We studied the incidence of intraoperative hypoxemia as well as that of pulse oximeter artifacts prospectively in 575 pediatric noncardiac surgery patients aged between 0 and 16 years operated in a tertiary pediatric university hospital. Subsequently, the incidence of intraoperative hypoxemia was determined retrospectively in 8277 patients registered in an anesthesia information management system (AIMS) of the same hospital. RESULTS:In the prospective cohort, at least 1 episode of oxygen saturation (SpO2) ⩽ 90% for at least 1 minute occurred in 69 of 575 cases (12%; 95% confidence interval [CI], 9%–15%). Furthermore, in 35 of 575 (6%; 95% CI, 4%–8%) cases at least 1 true hypoxemic event was observed. In total, 117 episodes of SpO2 ⩽ 90% were observed in the prospective study, of which 3 of 117 could not be specified and 67 of 114 (54%; 95% CI, 42%–65%) episodes were classified as true hypoxemia. False-positive low SpO2 values were mainly caused by dislodgment of the pulse oximeter. In the retrospective analysis, SpO2 ⩽ 90% and SpO2 ⩽ 80% for at least 1 minute were documented in the AIMS in 18% (95% CI, 17%–19%) and 7.5% (95% CI, 7%–8%) of the cases, respectively; 31 and 10 episodes per 100 cases, respectively. The incidence of hypoxemia increased in younger age groups: SpO2 ⩽ 90% for at least 1 minute occurred in 56% (95% CI, 49%–63%) of neonates (170 episodes per 100 cases). CONCLUSIONS:The incidence of intraoperative hypoxemia increased with younger age, with the highest incidence in neonates. Because of the high artifact rate, unvalidated pulse oximeter data in AIMS should be interpreted with caution because only up to 65% of all hypoxemic episodes recorded during pediatric anesthesia were caused by true hypoxia.

Effects of morphine and naloxone on thresholds of ventral tegmental electrical self-stimulation.

SummaryThe involvement of opioid systems in self-stimulation reward was investigated by studying the effects of the opioid antagonist naloxone (10 mg/kg s.c.) and graded doses of morphine (0.3–5.0 mg/kg s.c.) on intracranial electrical self-stimulation (ICSS) in rats with electrodes in the ventral tegmental area. Lever pressing for ICSS was analyzed using three different procedures: (1) determination of response rate i.e. the number of responses to high and threshold currents, (2) measuring threshold current when response rate was kept low and relatively constant, (3) determination of ‘behavioural’ threshold using a two-lever procedure in which a response on one lever resulted in a reset of the decreasing current to a high current contingent on a response to the other lever. It was found that low doses of morphine increased the response rate of ICSS behaviour and decreased the threshold whereas the higher doses decreased the response rate but also decreased the threshold current when measured with a rate insensitive procedure. Naloxone raised the threshold for ICSS and caused a corresponding decrease of response rate.In a second series of experiments in which the behaviour of rats which had been tested in one procedure was analysed using one of the other methods, it was observed that naloxone caused smaller changes, while the effects of morphine were at least comparable to those observed in the first series of experiments.The present data suggest that response rate insensitive procedures to analyse ICSS should be preferred to response rate sensitive ones, especially when the interaction of depressant drugs such as morphine with reward mechanisms is investigated. It is concluded that opioid systems are involved in ICSS elicited by electrical stimulation in the ventral tegmental area, and that the synergistic action of electrical stimulation and the pharmacological activation of ICSS reward circuits due to morphine may be related to the addictive properties of this drug.

A prospective randomized trial of acute tocolysis in term labour with atosiban or ritodrine

OBJECTIVEnTo study the effects of the tocolytics atosiban and ritodrine in term labour.nnnSTUDY DESIGNnWomen in term labour, requiring acute tocolysis, were prospectively randomized for treatment with either atosiban i.v. (n=70) or ritodrine i.v. (n=70). There were three indications for acute tocolysis: (1) fetal distress followed by continuation of labour, (2) fetal distress followed by emergency caesarean section (CS), and (3) arrest of contractions in women waiting for a secondary CS in the absence of fetal distress. Primary endpoints were maternal blood pressure (MBP) and maternal heart rate (MHR). Secondary endpoints were intra-uterine pressure, fetal heart rate (FHR), 5-Apgar score and umbilical arterial pH.nnnRESULTSnBaseline characteristics did not differ between the study groups. The ritodrine group showed a significant rise in MHR (p<0.001), MHR remained unaltered in the atosiban group (p=0.31). No significant changes occurred in systolic and diastolic BP in either group. FHR rose by a maximum of 11.6 bpm (8.5%) in the ritodrine group (p<0.001) compared to a rise of 4.9 bpm (4.8%) in the atosiban group (p=0.27). No differences were found in blood loss and fetal outcome. Compared to baseline, uterine pressure was reduced by a maximum of 55% (p<0.001) after ritodrine administration, compared to a maximal reduction of 54% (p<0.001) after atosiban administration. These effects did not differ between the two treatment groups.nnnCONCLUSIONnConsidering the maternal effects, our results suggest a possible role for atosiban bolus in acute tocolysis in term labour.

Adaptation of Clinical Prediction Models for Application in Local Settings

Background. When planning to use a validated prediction model in new patients, adequate performance is not guaranteed. For example, changes in clinical practice over time or a different case mix than the original validation population may result in inaccurate risk predictions. Objective. To demonstrate how clinical information can direct updating a prediction model and development of a strategy for handling missing predictor values in clinical practice. Methods. A previously derived and validated prediction model for postoperative nausea and vomiting was updated using a data set of 1847 patients. The update consisted of 1) changing the definition of an existing predictor, 2) reestimating the regression coefficient of a predictor, and 3) adding a new predictor to the model. The updated model was then validated in a new series of 3822 patients. Furthermore, several imputation models were considered to handle real-time missing values, so that possible missing predictor values could be anticipated during actual model use. Results. Differences in clinical practice between our local population and the original derivation population guided the update strategy of the prediction model. The predictive accuracy of the updated model was better (c statistic, 0.68; calibration slope, 1.0) than the original model (c statistic, 0.62; calibration slope, 0.57). Inclusion of logistical variables in the imputation models, besides observed patient characteristics, contributed to a strategy to deal with missing predictor values at the time of risk calculation. Conclusions. Extensive knowledge of local, clinical processes provides crucial information to guide the process of adapting a prediction model to new clinical practices.

Long-term changes in self-stimulation threshold by repeated morphine and naloxone treatment

To analyse the interaction between endogenous opioid systems and brain reward, the influence of repeated treatment for 3 weeks with morphine and the opioid antagonist naloxone was investigated in rats with self-stimulation electrodes in the ventral tegmental area. Changes in threshold of self-stimulation determined by a response rate insensitive two lever method were considered as changes in reward. Morphine induced a temporary decrease of the response rate which lasted 3 days, and decreased the threshold for self-stimulation. The effect on threshold remained present till morphine treatment was discontinued, indicating that tolerance does not develop to this effect of morphine. Repeated naloxone treatment gradually increased the threshold for self-stimulation. This effect persisted after discontinuation of naloxone treatment. It is concluded that blockade of opioid receptors induces long term changes in the setpoint of self-stimulation reward.