DANISH II 1986.

Methods	Multi‐centre study (Denmark). Method of allocation / randomization: closed envelopes numbered consecutively, and statistical tables of randomized numbers were used. Duration of treatment: 4 h Follow‐up:24 hrs
Participants	52 patients with hypertensive encephalopathy * Inclusion criteria: Patients with diastolic blood pressure of 135 mm Hg or greater associated with cerebral symptoms (headache, consciousness disturbances, paresis, paresthesia, dizziness, blurred vision, nausea and vomits). The distribution of patients with those symptoms was not reported according to randomized group * Exclusion criteria: Aged over 70 years, cerebral apoplexy with hemiparesis, subarachnoidal haemorrhage, ischaemic heart disease, pulmonary oedema, uremia , creatinine > 500mcmol/l, pregnancy) * Base‐line characteristics for the two randomized groups: Diazoxide (D) group: n= 28 Dihydralazine (H) group: n=24 Mean age in years (range ) D:54 (33‐69) H: 52 (27‐69) Gender F/M D: 6/22 H:10/14 Hx of HTN D: 14/28 (50%) H: 9/24 (38%) Note: Twelve out of 64 patients achieved DBP levels of <125 mmHg within one hour after 40 mg of IV furosemide. These patients were not randomized but followed. We did not include these patients in our review. As such: 64‐12= 52
Interventions	Diazoxide (D): n=28 Dihydralazine (H): n=24 Dose regimen: Diazoxide (D): two subgroups: A‐initial dose 75 mg IV then 150 mg IV every 15 min to reach DBP 110 mm Hg or max dose of 600 mg (12 patients). B‐ initial dose 75 mg then 75 mg every 30 min to reach DBP 110 mm Hg or max dose of 375 mg (16 patients) Dihydralazine (H): initial dose 6.25 mg I.M., then 12.5 mg I.M., every 30 min to reach DBP 110 mm Hg or max dose of 56.3 mg (24 patients)
Outcomes	Outcomes obtained from this trial for the two randomized groups: Diazoxide (D): n=28 Dihydralazine (H): n=24 Total SAE: NR Mortality Two deaths: However, the group to which the dead patients were originally allocated was not reported. One died from stroke at day 12, the other died from rupture of aortic aneurism at day 10. Total Non‐fatal CVE:NR Individual CVE: AMI: Diazoxide =1/28 Hydralaline=1 /24 Withdrawals due to adverse events: NR Blood pressure: Except for the end point SBP/DBP values given in text (page 15 & 18; for dihydralazine, diazoxide groups, respectively), data was obtained from graphs, fig2, reported in page 18.The calculated weighted mean BP change was: Diazoxide: SBP ‐29.63± NR; DBP ‐21.63±NR Dihydralazine: SBP ‐43.40±NR; DBP ‐36.09±NR Standard deviation of the change was not reported. In this case we imputed (according to our hierarchy) from other trials (any drug any dose) as there was no report whatsoever regarding SBP or DBP variability in this trial (including all publications). However, on page 19 fig.3 there is a plot for MAP change according to groups. The calculated MAP variability (SD) for diazoxide group 19.46, and 22.25 for the dihydralazine group. Heart rate: There is no report on heart rate in the original or duplicate publications
Notes	Funding: Not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Low risk	A ‐ Adequate