Validation of non-invasive arterial pressure monitoring during carotid endarterectomy.

BACKGROUND: Patients undergoing carotid endarterectomy require strict arterial blood pressure (BP) control to maintain adequate cerebral perfusion. In this study we tested whether non-invasive beat-to-beat Nexfin finger BP (BPfin) can replace invasive beat-to-beat radial artery BP (BPrad) in this setting. METHODS: In 25 consecutive patients (median age 71 yr) scheduled for carotid endarterectomy and receiving general anaesthesia, BPfin and BPrad were monitored simultaneously and ipsilaterally during the 30-min period surrounding carotid artery cross-clamping. Validation was guided by the standard set by the Association for the Advancement of Medical Instrumentation (AAMI), which considers a BP monitor adequate when bias (precision) is <5 (8) mm Hg, respectively. RESULTS: BPfin vs BPrad bias (precision) was -3.3 (10.8), 6.1 (5.7) and 3.5 (5.2) mm Hg for systolic, diastolic, and mean BP, respectively. One subject was excluded due to a poor quality BP curve. In another subject, mean BPfin overestimated mean BPrad by 13.5 mm Hg. CONCLUSION: Mean BPfin could be considered as an alternative for mean BPrad during a carotid endarterectomy, based on the AAMI criteria. In 23 of 24 patients, the use of mean BPfin would not lead to decisions to adjust mean BPrad values outside the predefined BP threshold. CLINICALTRIALSGOV: NCT01451294.

Perioperative hospital mortality at a tertiary paediatric institution.

BACKGROUND: Research in postoperative mortality is scarce. Insight into mortality and cause of death might improve and innovate perioperative care. The objective for this study was to report the 24-hour and 30-day overall, and surgery and anaesthesia-related, in-hospital mortality at a tertiary paediatric hospital. METHODS: All patients <18 yr old who underwent anaesthesia with or without surgery between January 1, 2006, and December 31, 2012, at the Wilhelmina Children's Hospital, Utrecht, The Netherlands, were included in this retrospective cohort study. Causes of death within 30 days were identified and tabulated into four major categories according to principal cause. RESULTS: A total of 45,182 anaesthetics were administered during this 7-yr period. The all-cause 24-hour hospital mortality was 13.1 per 10,000 anaesthetics (95% CI: 9.9-16.8) and the all-cause 30-day in-hospital mortality was 41.6 per 10,000 anaesthetics (95% CI: 35.9-48.0). In total five patients were partially contributable to anaesthesia (30-day mortality: 1.1/10,000, 95% CI: 0.4-2.6) and four patients were partially contributable to surgery (30-day mortality: 0.9/10,000, 95% CI: 0.2-2.3). Mortality was higher in neonates and infants, children with ASA physical status III and IV, and emergency- and cardiothoracic surgery. CONCLUSIONS: Neonates and infants, children with ASA physical status III or poorer, and emergency- and cardiothoracic surgery are associated with a higher postoperative mortality. Anaesthesia- or surgery-related complications contribute to mortality in only a small amount of the deaths, indicating the relative safety of paediatric surgical and anaesthetic procedures.

Impact of adding therapeutic recommendations to risk assessments from a prediction model for postoperative nausea and vomiting.

BACKGROUND: In a large cluster-randomized trial on the impact of a prediction model, presenting the calculated risk of postoperative nausea and vomiting (PONV) on-screen (assistive approach) increased the administration of risk-dependent PONV prophylaxis by anaesthetists. This change in therapeutic decision-making did not improve the patient outcome; that is, the incidence of PONV. The present study aimed to quantify the effects of adding a specific therapeutic recommendation to the predicted risk (directive approach) on PONV prophylaxis decision-making and the incidence of PONV. METHODS: A prospective before-after study was conducted in 1483 elective surgical inpatients. The before-period included care-as-usual and the after-period included the directive risk-based (intervention) strategy. Risk-dependent effects on the administered number of prophylactic antiemetics and incidence of PONV were analysed by mixed-effects regression analysis. RESULTS: During the intervention period anaesthetists administered 0.5 [95% confidence intervals (CIs): 0.4-0.6] more antiemetics for patients identified as being at greater risk of PONV. This directive approach led to a reduction in PONV [odds ratio (OR): 0.60, 95% CI: 0.43-0.83], with an even greater reduction in PONV in high-risk patients (OR: 0.45, 95% CI: 0.28-0.72). CONCLUSIONS: Anaesthetists administered more prophylactic antiemetics when a directive approach was used for risk-tailored intervention compared with care-as-usual. In contrast to the previously studied assistive approach, the increase in PONV prophylaxis now resulted in a lower PONV incidence, particularly in high-risk patients. When one aims for a truly 'PONV-free hospital', a more liberal use of prophylactic antiemetics must be accepted and lower-risk thresholds should be set for the actionable recommendations.

Effects of the introduction of the WHO "Surgical Safety Checklist" on in-hospital mortality: a cohort study.

OBJECTIVE: To evaluate the effect of implementation of the WHO's Surgical Safety Checklist on mortality and to determine to what extent the potential effect was related to checklist compliance. BACKGROUND: Marked reductions in postoperative complications after implementation of a surgical checklist have been reported. As compliance to the checklists was reported to be incomplete, it remains unclear whether the benefits obtained were through actual completion of a checklist or from an increase in overall awareness of patient safety issues. METHODS: This retrospective cohort study included 25,513 adult patients undergoing non-day case surgery in a tertiary university hospital. Hospital administrative data and electronic patient records were used to obtain data. In-hospital mortality within 30 days after surgery was the main outcome and effect estimates were adjusted for patient characteristics, surgical specialty and comorbidity. RESULTS: After checklist implementation, crude mortality decreased from 3.13% to 2.85% (P = 0.19). After adjustment for baseline differences, mortality was significantly decreased after checklist implementation (odds ratio [OR] 0.85; 95% CI, 0.73-0.98). This effect was strongly related to checklist compliance: the OR for the association between full checklist completion and outcome was 0.44 (95% CI, 0.28-0.70), compared to 1.09 (95% CI, 0.78-1.52) and 1.16 (95% CI, 0.86-1.56) for partial or noncompliance, respectively. CONCLUSIONS: Implementation of the WHO Surgical Checklist reduced in-hospital 30-day mortality. Although the impact on outcome was smaller than previously reported, the effect depended crucially upon checklist compliance.

Feedback system to estimate the quality of outpatient preoperative evaluation records: an analysis of end-user satisfaction.

BACKGROUND: During preanaesthesia evaluation at an outpatient clinic, information is summarized and structured. We aimed to estimate the effectiveness of this process by determining the proportion of patients presenting for surgery who had valid preoperative anaesthesia assessment records, and also the proportion of patients with a record that contained sufficient information. METHODS: This study included all non-cardiac surgery procedures performed in adults in 2006 and 2007 in a university hospital. In each case, we asked the anaesthesiologist actually providing anaesthesia to assess the quality of the preoperative record on an electronic feedback form showing a predefined drop down menu and a free text box. The primary outcome was the proportion of procedures with a valid record (< 6 months old) that also contained sufficient and adequate information to safely provide anaesthesia. Secondly, all predefined remarks were assessed for relevance and the proportion of (relevant) remarks per individual anaesthesiologist was calculated. RESULTS: During the study period, 21 454 procedures were performed. A valid record was available in 20 700 procedures (97%). In 459 (2%) cases, a remark (mostly about not detected comorbidity) was given by the anaesthesia provider, of which 347 (76%) were assessed as 'relevant', resulting in 20 353 (95%) valid records containing sufficient and adequate information. Between individual anaesthesiologists, the percentage remarks ranged from 0.4% to 12.7%. CONCLUSIONS: On entering the operating theatre, 95% of elective surgery patients had a preanaesthesia evaluation record that contained sufficient and adequate information to safely provide anaesthesia. There was large variability in reporting remarks.

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.

Biotelemetry: adjustment of a telemetry system for simultaneous measurements of acute heart rate changes and behavioral events in unrestrained rats.

The radiotelemetry system described in this paper consists of an implantable transmitter and a receiver, connected to a microcomputer. The hardware and software belonging to Mini-Mitters, for the collection and analysis of heart rate (HR), core temperature (CT), and gross activity data, do not possess the flexibility to detect acute changes in HR nor to discriminate among simultaneously occurring different types of behavior. In order to study short-term changes in HR in response to stress or drugs, in relation to behavioral responses, an inexpensive computer interface and a software program (CARDIAQ) were developed to collect data from Mini-Mitters. The interface conveys the QRS signal, which is converted to a TTL pulse train, to the parallel printer adapter (LPT1) of an IBM-compatible computer. Heart rate is determined by measuring single interbeat intervals (IBI). The software controls the sampling schedule and stores the collected data in a format compatible with a commercial spreadsheet package. The program calculates the median IBI per s, mean +/- SD IBI, variance, skewness, and kurtosis of the IBI distribution. In addition, it enables simultaneous recording of behavior by entering data through the keyboard at the occurrence of each event. In this paper, we describe the CARDIAQ program and provide examples of its application together with the implantable transmitters in freely moving rats.

Catecholamines and endogenous opioids in ventral tegmental self-stimulation reward.

Midbrain dopaminergic pathways and opioid receptor systems have been implicated in the reward experienced in electrical intracranial self-stimulation behavior. In the present experiment, the influence of graded doses of the dopamine antagonist haloperidol and of the agonist cocaine were investigated on electrical self-stimulation reward, elicited by electrodes located in the ventral tegmental area. A threshold method, which is rather insensitive for aspecific motor effects, was applied to determine the reward of self-stimulation. The method allowed to determine simultaneously the rate of lever pressing for self-stimulation. All doses of haloperidol and cocaine were administered with and without the opioid antagonist naloxone, in order to investigate the interaction between dopaminergic and opioid modulation of reward. Haloperidol lowered and cocaine tended to increase the response rate, whereas cocaine but also haloperidol lowered the self-stimulation threshold. The effects appear to be dose-dependent. Naloxone did not interact with the effect of the drugs on threshold and it lowered the response rate, but in the haloperidol-treated rats only. It is concluded that dopamine is involved in the reward of electrical self-stimulation elicited from the ventral tegmental area and that this involvement is independent of endorphin systems, suggesting the existence of separate catecholamine and opioid mechanisms modulating brain reward.

Site of rewarding action of morphine in the mesolimbic system determined by intracranial electrical self-stimulation.

Systemic treatment with morphine has been shown to facilitate intracranial electrical self-stimulation reward elicited from the ventral tegmental area (VTA) as was determined using a response rate-insensitive threshold measurement. In the present experiment graded doses of morphine were microinjected into the mesolimbic system to determine the site of this morphine action. Morphine injected into the nucleus accumbens did not affect the threshold and response rate of self-stimulation by electrodes in the VTA, while relatively high doses of morphine injected into the VTA produced a long-lasting decrease of the threshold of self-stimulation by electrodes in the nucleus accumbens. It is concluded that morphine can facilitate self-stimulation when injected into the VTA, and that a concerted action of morphine on multiple brain sites may be involved in the interaction of the drug with brain reward.

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

The 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: determination of response rate i.e. the number of responses to high and threshold currents, measuring threshold current when response rate was kept low and relatively constant, 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential effect of naloxone on food and self-stimulation rewarded acquisition of a behavioral response pattern.

The involvement of endogenous opioids in self-stimulation reward was investigated by repeated administration of the opioid antagonist naloxone to rats during acquisition of a behavioral response pattern that was rewarded with electrical (self-)stimulation of the ventral tegmental area. A control experiment was performed using food deprived rats in which a comparable response pattern was rewarded with food pellets. The response patterns consisted of gradually decreasing amounts of reward per response, which could be reset to maximal reward by another response. It was found that naloxone disrupted the acquisition of the stimulation rewarded response pattern, while it did not influence the food rewarded behavior. It is suggested that endorphin systems are actively involved in the acquisition of self-stimulation reward procedures, and that this involvement may be specific for self-stimulation reward.

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.

Hippocampus modulates self-stimulation reward from the ventral tegmental area in the rat.

Rats with electrodes in the ventral tegmental area were tested for the threshold of intracranial reward using a rate insensitive self-stimulation procedure. It was found that an electrolytic lesion of a part of the dorsal hippocampus induced a marked decrease in the variation of thresholds across rats, while the mean reward level did not change. This indicates that a factor is removed, by the hippocampal lesion, which causes differences in reward between individual rats. It is suggested that the mesolimbic dopaminergic system is involved in this modulatory influence of the hippocampus on reward.

Electrical stimulation of the ventral tegmental area and catecholamine metabolism in discrete regions of the rat brain.

Data are presented which show a different pattern of dopamine and noradrenaline utilization in terminal regions of the A9 and A10 dopaminergic systems and in terminal regions of the dorsal noradrenergic bundle after electrical stimulation of the ventral tegmental area and an adjacent area. At the sites of the electrodes an enhanced turnover of noradrenaline was found. These results are discussed relating the location of the electrode sites and the location of the dopaminergic cell bodies A9 and A10 and catecholaminergic fibers passing through the MFB innervating forebrain and limbic structures. It is concluded that activation of parts of the A10 dopaminergic system and the A6 noradrenergic system is correlated with intracranial self-stimulation.

Comparative effects of the ACTH 4-9 analogue (ORG 2766), ACTH 4-10 and [D-Phe7] ACTH 4-10 on medial septal self-stimulation behaviour in rats.

Experiments were performed to examine the effects of various analogues of ACTH on electrical self-stimulation behaviour elicited from the medial septal area using an ascending or descending sequence of stimulus intensities within a session. When an ascending sequence of threshold multiples was used ACTH 4-10 and the ACTH 4-9 analogue (ORG 2766) enhanced level pressing for low intensity stimulation but attenuated self-stimulation at greater current intensities. The analogue ORG 2766 appeared to be a thousand times more potent than ACTH 4-10; [D-Phe7] ACTH 4-10 inhibited the response rate at threshold level but was inactive at greater current intensities. The same effect was found following administration of ORG 2766 in a dose which was 20 times greater (1 microgram/rat) than that used in the first experiments. Lever pressing was not affected by treatment with ACTH 4-10 or ORG 2766 when a descending sequence of stimulus intensities was used within a session. Thus, ACTH-related peptides may affect motivational processes involved in self-stimulation rather than the reward of the stimulation per se. It is suggested that although ORG 2766 mimicked the action of ACTH 4-10 this synthetic peptide may have additional behavioural properties.