The relationship between the effect-site concentration of propofol and sedation scale in children: a pharmacodynamic modeling study

Background Continuous infusion of propofol has been used to achieve sedation in children. However, the relationship between the effect-site concentration (Ce) of propofol and sedation scale has not been previously examined. The objective of this study was to investigate the relationship between the Ce of propofol and the University of Michigan Sedation Scale (UMSS) score in children with population pharmacodynamic modeling. Methods A total of 30 patients (aged 3 to 6 years) who underwent surgery under general anesthesia with propofol and remifentanil lasting more than 1 h were enrolled in this study. Sedation levels were evaluated using the UMSS score every 20 s by a 1 μg/mL stepwise increase in the Ce of propofol during the induction of anesthesia. The pharmacodynamic relationship between the Ce of propofol and UMSS score was analyzed by logistic regression with nonlinear mixed-effect modeling. Results The estimated Ce50 (95% confidence interval) of propofol to yield UMSS scores equal to or greater than n were 1.84 (1.54–2.14), 2.64 (2.20–3.08), 3.98 (3.66–4.30), and 4.78 (4.53–5.03) μg/mL for n = 1, 2, 3, and 4, respectively. The slope steepness for the relationship of the Ce versus sedative response to propofol (95% confidence interval) was 5.76 (4.00–7.52). Conclusions We quantified the pharmacodynamic relationship between the Ce of propofol and UMSS score, and this finding may be helpful to predict the sedation score at the target Ce of propofol in children. Trial registration http://www.clinicaltrials.gov (No.: NCT03195686, Date of registration: 22/06/2017).

Rapid arousal from anaesthesia after reversal of deep rocuronium-induced neuromuscular block with sugammadex in a neuroradiological procedure

We describe the case of a 42-year-old man undergoing elective embolisation of an arteriovenous malformation at the level of the right posterior cerebral artery under propofol anaesthesia. We used the SedLine Brain Function Monitor (Masimo) to titrate the anaesthetic depth with propofol. At the end of the procedure, the patient aroused from anaesthesia very rapidly after the reversal of deep neuromuscular block with sugammadex, despite still significant calculated doses of propofol at the effect site. This rapid arousal was monitored using the SedLine Brain Function Monitor.

An audit of high-dose and combination antipsychotic prescribing across the general adult inpatient wards in Mersey Care NHS Foundation Trust

AimsTo review the number of prescriptions of regular high-dose antipsychotics and combination antipsychotic therapy across the eight general adult inpatient wards in Mersey Care NHS Foundation Trust and examine whether these prescriptions followed Trust recommendations for high-dose antipsychotic therapy (HDAT).BackgroundThe two main rationales behind prescribing HDAT are pharmacokinetics differ in individuals and so insufficient amounts of antipsychotic may reach the effect site at maximum dose in some patients and variations in the effect site between patients may mean higher doses are required to achieve therapeutic effect.MethodThe electronic prescription records for all patients on the eight general adult inpatient wards were scrutinised. 121 patients were prescribed antipsychotic medication. Any patients on a combination of regular antipsychotic medication or on HDAT were identified. Any patient on combination therapy or HDAT was studied to determine if Clozapine had been considered. The electronic notes of HDAT patients were analysed to ascertain whether tests recommended by Trust guidelines – BMI, blood pressure (B.P), pulse rate, ECG, FBC, U and Es, LFTs, serum prolactin, serum cholesterol and HbA1c level had been performed prior to initiation and following any dose increase.Result21 of 121 patients prescribed antipsychotic medication were on combination therapy. 11 were subject to HDAT. 8 of the 11 HDAT patients were on combination therapy. Clozapine was considered before initiating HDAT in 9 of the HDAT patients. Clozapine was considered in 13 of the 21 patients on combination antipsychotic therapy, but only two were initiated on Clozapine (combined with Olanzapine or Risperidone).100% of HDAT patients had an ECG prior to initiation of HDAT; only 36% had one after dose increases above BNF maximum. 100% of HDAT patients had their BMI measured before initiation. 91% had baseline B.P and heart rate checked. Of the recommended blood tests, 100% of HDAT patients had baseline FBC, U and Es, LFTs and serum cholesterol. Fewer patients had a baseline HbA1c level (91%) or serum prolactin (46%) measured.ConclusionPrevalence of HDAT across the general adult inpatient wards in the Trust was 9%, much lower than the 28% reported in the HDAT audit completed by the Prescribing Observatory for Mental Health in 2012. Patients within Mersey Care are more likely to be prescribed combination therapy than HDAT. Not every HDAT patient has been considered for Clozapine. There is a need to ensure Trust monitoring guidelines for HDAT patients are being strictly adhered to.