Monitoring for valproate and phenytoin toxicity in hypoalbuminaemia: A retrospective cohort study.

AIMS: Equations to calculate albumin-adjusted total concentrations have been validated to correlate with measured free concentrations for both phenytoin and valproate, but there is a lack of data to assess correlation with clinical outcomes. We aimed to assess the association of hypoalbuminaemia and albumin-adjusted total concentrations with concentration-dependent toxicity for phenytoin and valproate and review the impact on management decisions following concentration monitoring in hypoalbuminaemia. METHODS: Patients undergoing concentration monitoring for phenytoin or valproate between January and December 2018 were included. Patients were identified using a centralised laboratory database with data extracted from medical records. RESULTS: Total phenytoin concentrations were measured for 144 patients, with hypoalbuminaemia (≤30 g L-1 ) recorded in 59 (41%) patients. Albumin-adjusted phenytoin concentration >20 mg L-1 was associated with increased neurological adverse effects (77% vs. 43%, P < .001). On logistic regression, higher albumin-adjusted phenytoin concentration was an independent risk factor for neurotoxicity (OR 1.06, 95% CI 1.01-1.12, P = .011). Total valproate concentrations were measured for 383 patients, with hypoalbuminaemia (≤30 g L-1 ) noted in 53 (14%) patients. For the valproate cohort, hypoalbuminaemia (42% vs. 28%, P = .039) and albumin-adjusted valproate concentration >100 mg L-1 (49% vs. 23%, P < .001) were both associated with increased neurotoxicity. On multiple logistic-regression, valproate daily dose (aOR = 1.01, 95% CI 1.00-1.02, P = .006) and albumin-adjusted valproate concentration (aOR 1.01, 95% CI 1.00-1.02, P = .033) were independent risk factors for neurotoxicity after accounting for confounders. CONCLUSION: While measuring free drug concentrations in hypoalbuminaemia would be ideal, the adjustment equations can help identify vulnerable patients needing further assessment of potential concentration-dependent toxicity.

Cost-effectiveness of term induction of labour using inpatient prostaglandin gel versus outpatient Foley catheter.

OBJECTIVE: Evaluating cost-effectiveness of induction of labour (IOL) using outpatient mechanical cervical ripening using a Foley catheter (OFC) compared to inpatient chemical ripening using prostin gel (IPG). STUDY DESIGN: Cost-effectiveness analysis from a hospital perspective alongside a RCT. Women in a metropolitan Australian maternity hospital with an unfavourable cervix requiring IOL at term were randomised to IPG (n = 51) or OFC (n = 50). Primary economic measures were mean patient costs, incremental cost per predelivery inpatient hour prevented, and incremental cost per vaginal delivery within 12 h of admission to the birthing unit. Bootstrapping estimates were used to construct 95% confidence intervals. Estimates of net monetary benefit were calculated to aid interpretation of the results. RESULTS: Mean hospital costs per woman were nonsignificantly higher ($6524 OFC vs $5876 IPG) and mean difference $643; 95% CI -$366 to $1652. OFC group experienced fewer predelivery inpatient hours, resulting in an incremental cost per inpatient hour prevented of $57 (95% CI -$79.44 to $190.65). However, OFC patients were less likely to deliver vaginally within 12 h of admission to birthing unit. Other cost influencing clinical outcomes, including caesarean section rates and total inpatient hours, were not statistically different. Results were not sensitive to changes in costs or the cost-effectiveness thresholds. CONCLUSION: OFC had fewer inpatient hours and costs prior to birth. However, OFC did not reduce overall inpatient hours and failed to achieve comparable rates of vaginal delivery within 12 h of birthing unit admission. Therefore, OFC is unlikely to be considered cost-effective compared to IPG in current hospital settings.

Recruitment difficulties in obstetric trials: a case study and review.

BACKGROUND: The CONSORT statement calls for complete data on flow of participants, including all losses and exclusions. Incomplete reporting of flow into trials versus flow through trials is not uncommon. Where complete data exist in obstetric trials, poor recruitment seems a recurring theme. AIMS: To explore difficulties in recruitment and differences between assessed-but-not-recruited and included women to improve future trial participation, using a case study of a recently published randomised trial of outpatient Foley catheter versus inpatient PGE2 gel for cervical ripening. MATERIALS & METHODS: The assessed-but-not-recruited population of an obstetric trial (ACTRN:12609000420246) was prospectively studied for reasons for noninclusion, demographic data and pregnancy outcome. Women assessed-but-not-recruited due to declined consent or obstetrician declined participation were compared to included women. Main outcome measures included demographic and outcome differences associated with trial participation. RESULTS: Of 468 assessed participants, 220 (47%) were not eligible by exclusion criteria (potential 'trial factor' recruitment difficulties), 147 (31%) declined consent (n = 100, 'participant factor') or their obstetrician declined participation (n = 47, 'clinician factor') and 101 (22%) were included. Declining women were more likely than participants to be parous (24 vs 10%, P < 0.05), induced for nonmedical reasons (18 vs 4%, P < 0.001), privately admitted (31 vs 3%, P < 0.001) and have longer inpatient stay (4.9 vs 4.2 days, P < 0.05). CONCLUSION: The high assessed-but-not-recruited rate highlights important issues with external validity and feasibility when conducting obstetric trials, including recruitment difficulties related to participant, clinician and trial factors. Assessed: recruited ratios and demographic and outcome differences need consideration in planning and interpretation of randomised trials.

Outpatient Foley catheter versus inpatient prostaglandin E2 gel for induction of labour: a randomised trial.

BACKGROUND: Induction of labour (IOL) is one of the commonest obstetric interventions, with significant impact on both the individual woman and health service delivery. Outpatient IOL is an attractive option to reduce these impacts. To date there is little data comparing outpatient and inpatient IOL methods, and potential safety concerns (hyperstimulation) if prostaglandins, the standard inpatient IOL medications, are used in the outpatient setting. The purpose of this study was to assess feasibility, clinical effectiveness and patient acceptability of outpatient Foley catheter (OPC) vs. inpatient vaginal PGE2 (IP) for induction of labour (IOL) at term. METHODS: Women with an unfavourable cervix requiring IOL at term (N=101) were randomised to outpatient care using Foley catheter (OPC, n=50) or inpatient care using vaginal PGE2 (IP, n=51). OPC group had Foley catheter inserted and were discharged overnight following a reassuring cardiotocograph. IP group received 2 mg/1 mg vaginal PGE2 if nulliparous or 1 mg/1 mg if multiparous. Main outcome measures were inpatient stay (prior to birth, in Birthing Unit, total), mode of birth, induction to delivery interval, adverse reactions and patient satisfaction. RESULTS: OPC group had shorter hospital stay prior to birth (21.3 vs. 32.4 hrs, p< .001), IP were more likely to achieve vaginal birth within 12 hours of presenting to Birthing Unit (53% vs. 28%, p= .01). Vaginal birth rates (66% OPC Vs. 71% IP), total induction to delivery time (33.5 hrs vs. 31.3 hrs) and total inpatient times (96 hrs OPC Vs. 105 hrs IP) were similar. OPC group felt less pain (significant discomfort 26% Vs 58%, p=.003), and had more sleep (5.8 Vs 3.4 hours, p< .001), during cervical preparation, but were more likely to require oxytocin IOL (88 Vs 59%, p=.001). CONCLUSIONS: OPC was feasible and acceptable for IOL of women with an unfavourable cervix at term compared to IP, however did not show a statistically significant reduction in total inpatient stay and was associated with increased oxytocin IOL. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN:12609000420246.

Oral potassium overdose: a case series.

OBJECTIVE: Severe toxicity from ingestions of oral sustained-release potassium is rare. While acute hyperkalaemia requires urgent intervention given the risk of cardiac toxicity, there is a lack of clinical consensus on optimal management. The aim of this study was to characterise the clinical manifestations of acute potassium overdose and its management approach. METHODS: This is a retrospective case series of patients presenting following oral potassium overdose of ≥6000mg between January 2009 and December 2020 in Queensland, Australia as recorded in the state's Poisons Information Centre database and a tertiary Clinical Toxicology Unit database. Patients were identified from prospective databases maintained by both units and data were extracted from these in addition to medical records. RESULTS: Thirteen presentations in eleven patients occurred in the twelve-year period. The median age was 35 years (range 14-55 years). The median dose ingested was 6.4 mmol/kg (range 0.9-30.8 mmol/kg). Severe hyperkalaemia >7mmol/L occurred in five patients, four with ingestions ≥60,000mg. All patients with hyperkalaemia received multiple modes of intracellular potassium shifting therapy. Four patients had endoscopic removal of pharmacobezoars. One also underwent whole bowel irrigation. Three presentations were managed with haemodialysis. All patients were discharged home with a median length of stay of 20 h. CONCLUSION: Aggressive medical therapy to shift potassium into cells appears to be the mainstay of treatment in patients with normal renal function. Early decontamination may limit peak potassium concentrations. It is unclear if haemodialysis provides significant additional benefit in patients with normal renal function.