Valproic acid as adjuvant treatment for convulsive status epilepticus: a randomised clinical trial.

BACKGROUND: Generalised convulsive status epilepticus (GCSE) is a medical emergency. Guidelines recommend a stepwise strategy of benzodiazepines followed by a second-line anti-seizure medicine (ASM). However, GCSE is uncontrolled in 20-40% patients and is associated with protracted hospitalisation, disability, and mortality. The objective was to determine whether valproic acid (VPA) as complementary treatment to the stepwise strategy improves the outcomes of patients with de novo established GCSE. METHODS: This was a multicentre, double-blind, randomised controlled trial in 244 adults admitted to intensive care units for GCSE in 16 French hospitals between 2013 and 2018. Patients received standard care of benzodiazepine and a second-line ASM (except VPA). Intervention patients received a 30 mg/kg VPA loading dose, then a 1 mg/kg/h 12 h infusion, whilst the placebo group received an identical intravenous administration of 0.9% saline as a bolus and continuous infusion. Primary outcome was proportion of patients discharged from hospital by day 15. The secondary outcomes were seizure control, adverse events, and cognition at day 90. RESULTS: A total of 126 (52%) and 118 (48%) patients were included in the VPA and placebo groups. 224 (93%) and 227 (93%) received a first-line and a second-line ASM before VPA or placebo infusion. There was no between-group difference for patients hospital-discharged at day 15 [VPA, 77 (61%) versus placebo, 72 (61%), adjusted relative risk 1.04; 95% confidence interval (0.89-1.19); p = 0.58]. There were no between-group differences for secondary outcomes. CONCLUSIONS: VPA added to the recommended strategy for adult GCSE is well tolerated but did not increase the proportion of patients hospital-discharged by day 15. TRIAL REGISTRATION NO: NCT01791868 (ClinicalTrials.gov registry), registered: 15 February 2012.

Staged laparoscopic adjuvant intraperitoneal chemohyperthermia after complete resection for locally advanced colorectal or gastric cancer: a preliminary experience.

BACKGROUND: Cytoreductive surgery followed by intraperitoneal chemohyperthermia (IPCH) is a promising treatment for patients with peritoneal carcinomatosis, a disease with dismal prognosis. METHODS: We describe our preliminary experience with staged adjuvant laparoscopic IPCH after complete resection in patients with locally or regionally advanced colorectal or gastric cancer. RESULTS: Twenty-one patients underwent resection for colorectal (N = 16) or gastric cancer (N = 5) followed by staged laparoscopic IPCH. No conversion to laparotomy was required. No major operative incident occurred. Mean duration of hospital stay was 12 days (range 9-23 days). No mortality occurred in the 30-day postoperative period. Four patients developed major complications (19%). One patient (5%) was reoperated. Mean follow-up period was 15.5 months (range 9-29 months). Three patients died, including two of cancer-related causes. No patient developed peritoneal carcinomatosis during the follow-up period. CONCLUSION: Staged laparoscopic adjuvant IPCH after open or laparoscopic resection in selected patients with colorectal or gastric cancer is feasible and reasonably safe. However, additional data are required to determine the effect on long-term survival.