Transdermal glyceryl trinitrate lowers blood pressure and maintains cerebral blood flow in recent stroke. The effects of transdermal glyceryl trinitrate, a nitric oxide donor, on blood pressure, cerebral and cardiac hemodynamics, and plasma nitric oxide levels in acute stroke. The effect of transdermal glyceryl trinitrate, a nitric oxide donor, on blood pressure and platelet function in acute stroke. Propylene glycol toxicity following continuous etomidate infusion for the control of refractory cerebral edema. Bendrofluazide fails to reduce elevated blood pressure levels in the immediate post-stroke period. Low-dose vasopressin in the treatment of vasodilatory septic shock. Prophylactic phenylephrine infusion for preventing hypotension during spinal anesthesia for cesarean delivery. Ephedrine and phenylephrine for avoiding maternal hypotension due to spinal anaesthesia for caesarean section. Effects on uteroplacental and fetal haemodynamics. Should hypertension be treated after acute stroke? A randomized controlled trial using single photon emission computed tomography.
High blood pressure (BP) is common in acute stroke and is independently associated with a poor outcome. Lowering BP might improve outcome if it did not adversely affect cerebral blood flow (CBF) or cerebral perfusion pressure. We investigated the effect of glyceryl trinitrate ([GTN] an NO donor) on quantitative CBF, BP, and cerebral perfusion pressure in patients with recent stroke. Eighteen patients with recent (<5 days) ischemic (n=16) or hemorrhagic (n=2) stroke were randomly assigned (2:1) to transdermal GTN (5 mg) or control. CBF (global, hemispheric, arterial territory, and lesion, using xenon computed tomography) and BP (peripheral and central) were measured before and 1 hour after treatment with GTN. The effects of GTN on CBF and BP were adjusted for baseline measurements (ANCOVA). GTN lowered peripheral systolic BP by (mean) 23 mm Hg (95% CI, 2 to 45; P=0.03) and central systolic BP by 22 mm Hg (95% CI, 0 to 44; P=0.048). In contrast, GTN did not alter CBF (mL/min per 100 g): global -1.2 (95% CI, -6.5 to 4.2; P=0.66) and ipsilateral hemisphere -1.4 (95% CI, -7.6 to 4.9; P=0.65) or area of stroke oligemia, penumbra, or core (as defined by critical CBF limits). Contralateral CBF did not change: hemisphere 0 (95% CI, -7 to 6; P=0.96). GTN did not alter cerebral perfusion pressure or zero-filling pressure. Significant reductions in BP after transdermal GTN are not associated with changes in CBF or cerebral perfusion pressure or cerebral steal in patients with recent stroke. Trials need to assess the effect of lowering BP on functional outcome. High blood pressure in acute stroke is common and appears to be associated with a poor outcome. Lowering blood pressure might therefore improve outcome, provided that cerebral perfusion is not compromised. We assessed the effects of glyceryl trinitrate (GTN) on cerebral and systemic hemodynamic measures in acute stroke. Ninety patients with acute ischemic or hemorrhagic stroke were randomized within 72 hours of ictus to transdermal GTN given daily for 10 days (either 5 mg, 5 mg for 4 days then 10 mg, or 10 mg) or control. Twenty-four hour blood pressure monitoring, middle cerebral artery blood velocity, cardiac output, augmentation index, and plasma nitric oxide levels were each measured at baseline and then on days 1, 4, 5, and 10. The primary outcome was blood pressure on day 1. We found that GTN lowered mean peripheral arterial blood pressure on day 1 by 5.3% to 6.7% in a dose dependent manner as compared with control (mean, SD): control, 108.8 (15.1) mmHg; 5 mg, 102.5 (13.9) mmHg; 5/10 mg, 103.4 (14.9) mmHg; 10 mg, 101.5 (12.6) mmHg; (P = .005). Increasing the dose from 5 to 10 mg on day 5 resulted in an overall reduction in blood pressure of 11.4% as compared with leaving the dose at 5 mg (P = .006). GTN reduced peripheral pulse pressure, central aortic blood pressure, pulse pressure, and augmentation index on day 1. Middle cerebral artery blood velocity and pulsatility index in the affected hemisphere, cardiac output, systemic peripheral resistance, and plasma nitric oxide levels were not altered by GTN. Treatment with GTN was associated with headache: control 0 (0%), GTN 9 (15%) (P = .027); no negative effect on end-of-treatment death or deterioration, or 3 month death or dependency was discernable. GTN reduced peripheral blood pressure in a dose-dependent fashion in patients with acute stroke at day 1 and also reduced central blood pressure and augmentation index. In contrast, GTN did not alter middle cerebral artery blood velocity or pulsatility index in the affected hemispheres, suggesting that cerebral blood flow did not change. A trial assessing the effect of lowering blood pressure with GTN on safety and functional outcome in patients with acute stroke is now warranted. Hypertension is a common medical complication in acute stroke and is associated with a poor outcome. However, no large trials have assessed the effect of lowering blood pressure (BP) on outcome, and it remains unclear how BP should be managed in acute stroke. We assessed, in a double-blind randomised controlled trial, whether the nitric oxide (NO) donor glyceryl trinitrate (GTN, a known systemic and cerebral vasodilator), would lower BP and alter platelet function.
                Thirty-seven patients with recent (< 5 days) ischaemic or haemorrhagic stroke were randomised by minimisation to 12 days of daily treatment with transdermal GTN or matching placebo patches. Twenty-four-hour ambulatory BP was measured before and during GTN treatment at days 0, 1 and 8. Platelet aggregation and expression of adhesion molecules were assessed at the same time points. Functional outcome (Rankin scale) and case fatality were assessed at 3 months. Analysis was by intention-to-treat.
                GTN significantly lowered BP by 13.0/5.2 mm Hg at day 1 and 9.3/5.0 mm Hg at day 8. The lesser reduction at day 8 than day 1 suggests that tolerance to GTN was developing. Non-significant falls of 0.9/0.6 and 3.8/0.0 mm Hg occurred at days 1 and 8, respectively, in the placebo group. GTN had no effect on heart rate, or platelet aggregation or expression of platelet adhesion molecules, including glycoproteins Ia, Ib, IIIa and P-selectin. Additionally, GTN did not alter case fatality or dependency, although the study was not powered for these outcomes.
                Transdermal GTN, an NO donor, lowered BP by 5-8%, a clinically significant and relevant, but not excessive, degree in patients with acute stroke. However, GTN had no effect on platelet aggregation or expression of adhesion molecules. Since NO donors increase cerebral blood flow in patients with acute ischaemic stroke, GTN may be an appropriate drug for testing the effect of lowering BP on functional outcome.
                Copyright 2001 S. Karger AG, Basel Continued elevations in Intracranial Pressure (ICP) following traumatic or ischemic compromise are known to cause markedly increased morbidity and mortality. Because of the side effects of barbiturates including hypotension and prolonged recovery time, the use of shorter-acting anesthetic agents to control ICP has been considered. Etomidate, when administered by continuous infusion, has been shown to decrease cerebral metabolism resulting in a secondary decrease in cerebral blood flow with minimal changes in cerebral perfusion pressure. We initially intended to randomize 20 patients prospectively into a study protocol that would assess the effects of either pentobarbital or the cardioprotective agent etomidate on ICP and cardiac performance. Given the sequelae of the therapy, we were only able to randomize seven patients with cerebral edema refractory to medical management to receive either etomidate or pentobarbital in a blinded fashion. Three patients who received etomidate developed renal compromise (mean low creatinine clearance 41 ml/min, range 37-44 ml/min) which was initially noted at 24 hours. We believed that this represented an adverse effect that was probably related to the study drug and the study was stopped. Each patient received a 0.30 mg/kg IV induction of etomidate and then 0.02 mg/kg/min continuous infusion for 24-72 hours titrated burst suppression. All patients also received dexamethasone 2 mg IV every six hours to prevent the adrenocortical insufficiency that might occur as a consequence of etomidate-induced suppression of cortisol synthesis. Intracranial pressure decreased (mean = 12mmHg) following the initiation of etomidate. Cardiac parameters remained unchanged (cardiac output 4.8 +/- .6 liters/min).(ABSTRACT TRUNCATED AT 250 WORDS) Blood pressure (BP) levels, beat-to-beat blood pressure variability, dynamic cerebral autoregulation and cardiac baroreceptor sensitivity are frequently abnormal following acute stroke and are associated with an adverse short- and long-term prognosis. Thiazide diuretics are effective antihypertensive agents in preventing primary and secondary stroke, but their hypotensive and cerebral autoregulatory effects in the immediate post-stroke period have not been studied.
                Thirty-seven hypertensive neuroradiologically proven ischaemic stroke patients were randomized in a double-blind, placebo controlled, parallel group study to bendrofluazide 2.5 mg daily or matching placebo, within 96 h of stroke onset, for a 7-day period. Casual and non-invasive beat-to-beat arterial BP levels, cerebral blood flow velocity, ECG and transcutaneous carbon dioxide levels were measured within 70 +/- 20 h of cerebral infarction and again 7 days later. Dynamic cerebral autoregulatory indices, pulse interval, BP variability and cardiac baroreceptor sensitivity were also calculated.
                Small, non-significant falls were seen in casual and beat-to-beat BP levels over the 7-day period in both active and placebo-treated patients with no differences between treatments. No significant changes were seen in dynamic cerebral autoregulation or in cardiac baroreceptor sensitivity during the follow-up in either group.
                Following acute ischaemic stroke, the standard dose of bendrofluazide at 2.5 mg daily in this study sample did not lower systemic BP levels over the subsequent 7-day period. There was no evidence that bendrofluazide significantly altered cerebral autoregulation or improved cardiac baroreceptor sensitivity post-ictus. Bendrofluazide appears to be an ineffective hypotensive agent at the standard dosage in the initial post-stroke period.
                Copyright 2005 S. Karger AG, Basel. Despite appropriate therapy, refractory hypotension often occurs in septic shock. A double-blinded placebo controlled clinical trial was performed to assess the role of low-dose vasopressin (VP) as a pressor agent in septic shock.
                Patients admitted to a trauma intensive care unit with vasodilatory septic shock were randomized to receive either VP at 0.04 U/min (n = 5) or placebo (n = 5). Vasodilatory septic shock was defined as a need for catecholamine agents to maintain a mean arterial pressure more than or equal to 70 mm Hg, despite a cardiac index more than 2.5 L/min and a minimal pulmonary artery wedge pressure more than 12 mm Hg. After 1 hour of initiation of the study drug, attempts to discontinue norepinephrine, phenylephrine, and/or dopamine, in respective order, were undertaken provided that the mean arterial pressure remained more than or equal to 70 mm Hg.
                A vasopressin infusion increased systolic arterial pressure (98 +/- 5 to 125 +/- 8 mm Hg, p < 0.008) because of peripheral vasoconstriction (systemic vascular resistance increased from 878 +/- 218 to 1,190 +/- 213 dynes/s per cm(-5) p < 0.05). Arterial pressure and systemic vascular resistance were statistically unaffected in the placebo group. Before study termination, measured at 24 hours after drug initiation, two patients in the placebo group died of refractory hypotension. However, all patients receiving VP survived the 24-hour study period and had all other catecholamine pressors withdrawn and blood pressure maintained solely with a low-dose VP infusion.
                A VP infusion improved arterial pressure and permitted the withdrawal of catecholamine vasopressors. VP is a useful agent in the treatment of refractory septic shock. In a randomized, double-blinded, controlled trial, we investigated the prophylactic infusion of IV phenylephrine for the prevention of hypotension during spinal anesthesia for cesarean delivery. Immediately after intrathecal injection, phenylephrine was infused at 100 microg/min (n = 26) for 3 min. From that point until delivery, phenylephrine was infused at 100 microg/min whenever systolic arterial blood pressure (SAP), measured each minute, was less than baseline. A control group (n = 24) received IV bolus phenylephrine 100 microg after each measurement of SAP <80% of baseline. Phenylephrine infusion decreased the incidence (6 [23%] of 26 versus 21 [88%] of 24; P < 0.0001), frequency, and magnitude (median minimum SAP, 106 mm Hg; interquartile range, 95-111 mm Hg; versus median, 80 mm Hg; range, 73-93 mm Hg; P < 0.0001) of hypotension compared with control. Heart rate was significantly slower over time in the infusion group compared with the control group (P < 0.0001). Despite a large total dose of phenylephrine administered to the infusion group compared with the control group (median, 1260 microg; interquartile range, 1010-1640 microg; versus median, 450 microg; interquartile range, 300-750 microg; P < 0.0001), umbilical cord blood gases and Apgar scores were similar. One patient in each group had umbilical arterial pH <7.2. Prophylactic phenylephrine infusion is a simple, safe, and effective method of maintaining arterial blood pressure during spinal anesthesia for cesarean delivery.
                In patients receiving spinal anesthesia for elective cesarean delivery, a prophylactic infusion of phenylephrine 100 microg/min decreased the incidence, frequency, and magnitude of hypotension with equivalent neonatal outcome compared with a control group receiving IV bolus phenylephrine. The effects of i.v. vasopressors on Doppler velocimetry of the maternal uterine and placental arcuate arteries and the fetal umbilical, renal and middle cerebral arteries were studied during spinal anaesthesia in 19 healthy parturients undergoing elective caesarean section. Fetal myocardial function was investigated at the same time by M-mode echocardiography. The patients were randomized into two groups, to be given either ephedrine or phenylephrine as a prophylactic infusion supplemented with minor boluses if systolic arterial pressure decreased by more than 10 mmHg from the control value. Both the vasopressors restored maternal arterial pressure effectively. The ephedrine group showed no significant differences in any of the Doppler velocimetry recordings relative to the baseline values, but during the phenylephrine infusion the blood flow velocity waveform indices for the uterine and placental arcuate arteries increased significantly and vascular resistance decreased significantly in the fetal renal arteries. Healthy fetuses seem to tolerate these changes in uteroplacental circulation well, however, since the Apgar scores for the newborns and the acid-base values in the umbilical cord were within the normal range in both groups. The results suggest that some caution is required when selecting the specific vasopressor agent, the dosage and the mode of administration for the treatment of maternal hypotension secondary to spinal anaesthesia for caesarean section. To determine if previously hypertensive patients with acute ischemic stroke should be treated with antihypertensive medication in the immediate poststroke period.
                Randomized double-blind, placebo-controlled trial.
                Sixteen consecutive hypertensive patients (four men and 12 women; mean age, 66 years [age range, 46 to 83 years]) with middle cerebral artery infarction within 72 hours of onset and blood pressure between 170 and 220 mm Hg(systolic) and 95 and 120 mm Hg (diastolic).
                Placebo (n = 6), nicardipine hydrochloride (20 mg [n = 5]), captopril (12.5 mg [n = 3]), or clonidine hydrochloride (0.1 mg [n = 2]) given every 8 hours for 3 days.
                Decline in blood pressure, change in cerebral blood flow as measured by single photon emission computed tomography, and clinical change as determined by the National Institutes of Health Stroke Scale.
                Blood pressure fell significantly in both the drug-treated group as a whole and in those patients receiving placebo (P < .001). There was no difference in blood pressure levels between these two groups throughout the study period. Patients receiving nicardipine had a consistently lower pressure than the other groups. A significant negative relationship was noted between the maximum blood pressure fall and improvement in cerebral blood flow. There were four patients whose blood pressure dropped by more than 16% of the baseline value on any 24 hours in the first 3 days. All either failed to increase or actually decreased their cerebral blood flow to the affected area. Three of these patients were treated with nicardipine. There was no significant difference in clinical course between the placebo-and drug-treated groups as a whole.
                Hypertensive ischemic stroke patients with a moderate elevation of blood pressure in the first few days may not require antihypertensive therapy. Nicardipine and possibly other calcium channel blockers may cause an excessive fall in blood pressure and impair cerebral blood flow in these patients and should therefore be used with caution.
There is insufficient evidence to evaluate the effect of altering blood pressure on outcome during the acute phase of stroke. In patients with acute stroke, CCBs, ACEI, ARA and GTN each lower blood pressure while phenylephrine probably increases blood pressure.