BACKGROUND:We compared plasma and cerebrospinal fluid (CSF) pharmacokinetics of paracetamol after intravenous (IV) and oral administration to determine dosing regimens that optimize CSF ...concentrations.
METHODS:Twenty-one adult patients were assigned randomly to 1 g IV, 1 g oral or 1.5 g oral paracetamol. An IV cannula and lumbar intrathecal catheter were used to sample venous blood and CSF, respectively, over 6 hours. The plasma and CSF maximum concentrations (Cmax), times to maximum concentrations (Tmax), and area under the plasma and CSF concentration-time curves (AUCs) were calculated using noncompartmental techniques. Significance was defined by P < .0167 (Bonferroni correction for 3 comparisons for each parameter). Probability (X < Y) (p″) with Bonferroni corrected 95% confidence intervals (CIs) were calculated (CIs including 0.5 meet the null hypothesis). Results are presented as median (range) or p″ (CI). P values are listed as 1 g IV vs 1 g orally, 1 g IV vs 1.5 g orally and 1 g orally vs 1.5 g orally, respectively.
RESULTS:Wide variation in measured paracetamol concentrations was observed, especially in the oral groups. The median plasma Cmax in the 1 g IV group was significantly greater than the oral groups. In contrast, the median CSF Cmax was not different between groups. The median plasma Tmax in the 1 g IV group was 105 and 75 minutes earlier than in the 1 and 1.5 g oral groups. The median CSF Tmax was not significantly different between groups. The median plasma AUC (total) was not significantly different between groups; however, in the first hour, the median plasma AUC was significantly greater in the IV group than in the oral groups. In the second hour, there was no difference between groups. The median CSF AUC (total) did not significantly differ between groups; however, in the first hour, the median CSF AUC was significantly greater in the IV compared with the orally groups. In the second hour, there was no difference between groups. Our analysis indicated that the median Cmax, Tmax, and AUC values lacked precision because of small sample sizes.
CONCLUSIONS:Peak plasma concentrations were greater and reached earlier after IV than oral dosing. Evidence for differences in CSF Cmax and Tmax was lacking because of the small size of this study.
There is a plausible pathophysiologic rationale for increased long-term cardiovascular morbidity and mortality in patients receiving significant exposure to nitrous oxide. However, this relationship ...has not been established clinically. The ENIGMA trial randomized 2050 patients having noncardiac surgery lasting more than 2 hours to nitrous oxide-based or nitrous oxide-free anesthesia. We conducted a follow-up study of the ENIGMA patients to evaluate the risk of cardiovascular events in the longer term.
The trial case report forms and medical records of all study patients were reviewed. The date and cause of death and occurrence of myocardial infarction or stroke were recorded. A telephone interview was then conducted with all surviving patients. The primary endpoint of the study was survival.
The median follow-up time was 3.5 (range: 0 to 5.7) years. Three hundred eighty patients (19%) had died since the index surgery, 91 (4.5%) were recorded as having myocardial infarction, and 44 (2.2%) had a stroke during the entire follow-up period. Nitrous oxide did not significantly increase the risk of death hazard ratio = 0.98 (95% confidence interval, CI: 0.80 to 1.20; P = 0.82). The adjusted odds ratio for myocardial infarction in patients administered nitrous oxide was 1.59 (95% CI: 1.01 to 2.51; P = 0.04) and for stroke was 1.01 (95% CI: 0.55 to 1.87; P = 0.97).
The administration of nitrous oxide was associated with increased long-term risk of myocardial infarction, but not of death or stroke in patients enrolled in the ENIGMA trial. The exact relationship between nitrous oxide administration and serious long-term adverse outcomes will require confirmation by an appropriately designed large randomized controlled trial.
Community harm associated with prescription opioids is causing global concern, and post-hospital discharge prescribing is contributing to the problem. We surveyed anaesthetists in Australia and New ...Zealand to determine which opioid stewardship measures are currently in place, and to gauge interest in participating in future health services research on introducing an opioid stewardship bundle of care. A total of 87 anaesthetists from 87 hospitals were invited to participate, and 45 (52%) responded. The extent of nine current opioid stewardship measures reported was highly variable. One respondent (2%) reported no measures introduced at their hospital; 12 (27%) one to two measures; 16 (36%) three or four measures; 13 (29%) five to seven measures; and 3 (7%), all nine measures were in place. Respondents were often interested in being contacted about future trial participation (n1/433, 73%); however, concerns regarding feasibility of introducing an opioid stewardship bundle of care were widespread (n1/422, 49%). It is possible that the variability in Australian and New Zealand opioid stewardship practice is due, in part, to the current limited evidence base for the individual measures, in addition to challenges in research translation. We have found that interest in further research on opioid stewardship is high. Comprehensive, locally adapted, evidence-based opioid stewardship measures may increase the safety of patients and the community following opioid therapy.
The practice of anaesthetists relating to the administration of intraoperative oxygen has not been previously quantified in Australia and New Zealand. The optimal regimen of intraoperative oxygen ...administration to patients undergoing surgery under general anaesthesia is not known, and international recommendations for oxygen therapy are contradictory; theWorld Health Organization (WHO) recommend administering an intraoperative fraction of inspired oxygen of at least 0.8, while the World Federation of Societies of Anaesthesiologists, British Thoracic Society, and Thoracic Society of Australia and New Zealand recommend a more restrictive approach. We conducted a prospective observational study to describe the pattern of intraoperative oxygen administration among anaesthetists in Australia and New Zealand and, second, to determine the proportion of anaesthetists who administer intraoperative inspired oxygen in accordance with the WHO recommendations. We identified 150 anaesthetists from ten metropolitan hospitals in Australia and New Zealand and observed the patterns of intraoperative oxygen administration to American Society of Anesthesiologists physical status classification (ASA) 3 or 4 patients undergoing prolonged surgery under general anaesthesia. The median (interquartile range) intraoperative time-weighted mean fraction of inspired oxygen (FiO2) for all participants in the study was 0.47 (0.40-0.55). Three out of 150 anaesthetists (2%, 95% confidence interval 0.4 to 5.7) administered an average intraoperative FiO2 of at least 0.8. These findings indicate that most anaesthetists routinely administer an intermediate level of oxygen for ASA 3 or 4 adult patients undergoing prolonged surgery in Australia and New Zealand, rather than down-titrating inspired oxygen to a target pulse oximetry reading (SpO2) or administering liberal perioperative oxygen therapy in line with the current WHO recommendation.
Deterioration after major surgery is common, with many patients experiencing a medical emergency team (MET) activation. Understanding the triggers for MET calls may help design interventions to ...prevent deterioration. We aimed to identify triggers for MET activation in non-cardiac surgical patients. A retrospective cohort study of adult patients who experienced a postoperative MET call at a single tertiary hospital was undertaken. The trigger and timing of each MET call and patient characteristics were collected.
Four hundred and one MET calls occurred after 23,258 surgical procedures, a rate of 1.7% of all non-cardiac surgical procedures, accounting for 11.7% of all MET calls over the study period. Hypotension (41.4%) was the most common trigger, followed by tachycardia (18.5%), altered conscious state (11.0%), hypoxia (10.0%), tachypnoea (5.7%), 'other' (5.7%), clinical concern (4.0%), increased work of breathing (1.5%) and bradypnoea (0.7%). Cardiac and/or respiratory arrest triggered 1.2% of MET activations. Eighty-six percent of patients had a single MET call, 10.2% had two, 1.8% had three and one patient (0.3%) had four. The median interval between post-anaesthetic care unit (PACU) discharge and MET call was 14.7 h (95% confidence interval 4.2 to 28.9 h). MET calls resulted in intensive care unit (ICU) admission in 40 patients (10%), while 82% remained on the ward, 4% had a MET call shortly after ICU discharge and returned there, 2% returned to theatre, and 2% went to a high dependency unit.
Hypotension was the most common trigger for MET calls after non-cardiac surgery. Deterioration frequently occurred within 24 h of PACU discharge. Future research should focus on prevention of hypotension and tachycardia after surgery.
The sedative drug combination that produces minimal cognitive impairment and optimal operating conditions during colonoscopy has not been determined. We sought to determine if the use of propofol ...alone results in less cognitive impairment at discharge than the use of propofol plus midazolam and/or fentanyl in patients presenting for elective outpatient colonoscopy.
Two hundred adult patients presenting for elective outpatient colonoscopy were randomized to receive propofol alone or propofol plus midazolam, and/or fentanyl for IV sedation. Baseline cognitive function was measured using the computerized CogState test battery (Cogstate, Melbourne, Australia) before sedation. During the procedure, sedative drug doses, depth of sedation (via the bispectral index and observer's assessment of alertness/sedation score), complications, and treatability were recorded. Patients were interviewed about recall immediately after emerging from sedation, and cognitive testing was repeated at hospital discharge. Recovery times, quality of recovery, and satisfaction with care were also recorded.
In the propofol plus adjuvants group, 84 patients received fentanyl 50 microg (25-100) (median range) and 57 patients received midazolam 2 mg (0.5-10). Patients' cognitive function at discharge was worse than their performance at baseline. However, the changes in cognitive function between discharge and baseline were not significantly different between the two groups. At discharge, 18.5% of patients were cognitively impaired to an extent equivalent to a blood-alcohol concentration of 0.05%. Sedation with propofol plus midazolam and/or fentanyl produced better operating conditions than sedation with propofol alone and was associated with shorter procedure times. Recovery times, recall, dreaming, quality of recovery, and patient satisfaction with care were similar between the groups. Administration of >2 mg of midazolam was a predictor of impaired cognitive function at discharge.
Significant cognitive impairment was common at discharge from elective outpatient colonoscopy. However, the addition of midazolam and/or fentanyl to propofol sedation did not result in more cognitive impairment than the use of propofol alone. Furthermore, the use of adjuvants improved the ease of colonoscopy without increasing the rate of complications or prolonging early recovery times..
...we conducted a survey of postoperative surgical patients’ attitudes regarding PONV and its treatment. Baseline demographic data included age, sex, elective versus emergency surgery and Apfel risk ...score (one point each for non-smoking status, prior history of PONV/motion sickness, female sex, and postoperative opioid use).5 We asked patients whether nausea or vomiting had been experienced postoperatively and whether, if a hypothetical future operation resulted in PONV, they would be likely to try a non-drug treatment in general, and chewing gum in particular. ...patient attitudes are favourable towards chewing gum as a potential non-drug treatment for PONV.
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