William F. Rutherford

Fenoldopam mesylate versus sodium nitroprusside in the acute management of severe systemic hypertension.

Thirty‐three patients with severe systemic hypertension defined as a diastolic blood pressure (DBP) ≥ 120 mm Hg were randomized in a single‐blind fashion to be treated with either intravenous fenoldopam mesylate (FNP) or sodium nitroprusside (NTP). Fenoldopam mesylate and NTP infusion rates began at 0.1 μg/kg/minute and 0.5 μg/kg/minute, respectively and were titrated to achieve a goal DBP of between 95 and 110 mm Hg; or a reduction of at least 40 mm Hg if the baseline DBP was > 150 mm Hg. Fenoldopam mesylate (n = 15) reduced blood pressure from 217/145 ± 6/5 to 187/112 ± 6/3 mm Hg (P < .001) at an average infusion rate of 0.5 ± 0.1 μg/kg/minute. The average time to achieve goal DBP with FNP was 1.5 ± 1.4 hours. Nitroprusside (n = 18) reduced blood pressure from 210/136 ± 5/2 to 172/103 ± 6/2 mm Hg (P < .001) at an average infusion rate of 1.2 ± .24 μg/kg/minute. Nitroprusside response time averaged 2 ± 2.5 hours. There was no significant difference between the magnitude of effect seen with either FNP or NTP; nor was there any difference observed in the adverse effect rates of the two agents. Fenoldopam mesylate and NTP demonstrate similar overall efficacy in the treatment of severe systemic hypertension.

Assessment of intravenous fenoldopam mesylate in the management of severe systemic hypertension.

To evaluate the acute BP response to iv fenoldopam mesylate (FNP), 14 patients with severe hypertension (diastolic BP 120 to 170 mm Hg) were studied in an open-label trial. Initial infusion rate of FNP was 0.1 microgram/kg.min. Titration to diastolic BP goal (95 to 110 mm Hg) was followed by a constant infusion phase (greater than or equal to 6 h), a detitration phase (2 h), and a postinfusion phase. FNP reduced BP by 27/29 mm Hg (p less than .001) with no significant effect on heart rate. Maintenance of the BP effect was noted through the 6 h of constant rate infusion. Mild, transient vasodilating-associated adverse effects were noted with FNP. We conclude that FNP is an effective, well-tolerated iv antihypertensive agent for acute BP reduction in a severely hypertensive population.

Hyperventilation-Induced Reduction in Cerebral Blood Flow: Assessment by Positron Emission Tomography

The use of positron emission tomography (PET) has been well documented as a relatively noninvasive method of measuring cerebral blood flow (CBF), both globally and regionally. The utility of readily detecting alterations in CBF is apparent, particularly when applied to the evaluation of therapeutic interventions thought to influence CBF. We report the effects of hypocapnia, an experimental condition of known cerebral vasoconstriction, in ten normal volunteers. Subjects had brain blood flow evaluated utilizing H2 15O as the positron emitter before and after approximately five minutes of hyperventilation. Baseline CBF was measured as a mean ± SD of 61.2 ± 16.3 mL/min/100 g of tissue. Mean baseline arterial blood gas values were PaO2 107.4 ± 14 mm Hg, PaCO2 37.7 ± 0.89 mm Hg, and pH 7.39 (calculated from mean [H+]). Post hyperventilation, global CBF was measured as 31.1 ± 10.8 mL/min/100 g. Mean arterial blood gas values were PaO2 141.7 ± 21 mm Hg, PaCO2 19.7 ± 5 mm Hg, and pH 7.63 (calculated from mean [H+]). CBF decreased by a mean of 49.5 ± 11 percent. Data analysis using the Students t-est showed a significant change over baseline in PaCO2 (p<0.001) and CBF (p<0.001), in the hyperventilated state. Correlations were noted between the decrease in CBF and change in PaCO2 (r = 0.81) as well as between hyperventilation PaCO2 and the change in CBF (r=0.97). We conclude that, as measured by PET, CBF decreases significantly during a state of artificial hyperventilation to a degree consistent with results seen using other methods. PET appears to be a valuable tool in the assessment of interventions that could influence CBF.

Report of nitropatch explosions complicating defibrillation

Reports of complications associated with the use of electrical defibrillators have been relatively rare. In two patients, defibrillation performed over a nitroglycerin skin patch resulted in electrical arcing with a resultant flash of light and thermal injuries. Skin burns as a complication of defibrillation over nitropatches has not been previously reported. Such burn injuries respond to standard therapeutic measures. Healthcare professionals who may perform defibrillation should be aware of this potential complication.

Comparative acute blood pressure reduction from intravenous fenoldopam mesylate versus sodium nitroprusside in severe systemic hypertension

Fenoldopam mesylate (SK&F 82526J) (FNP) is a specific postsynaptic dopamine-1 receptor agonist,1 with weak α2-antagonistic properties.2 The agent is devoid of dopamine-2, α-1 or β-adrenergic activity.3 Fenoldopam functions as an arteriolar vasodilator with dilation in the renal, mesenteric, skeletal muscle and lumbar beds.4,5 Although a primary effect is through renal vasodilation with consequent increases in renal blood flow,1–2,4–6 reduction in total peripheral resistance appears to be the mechanism of blood pressure (BP) reduction.7,8 Furthermore, fenoldopam improves renal blood flow, fractional sodium and free water clearance while lowering BP.4,9,10 Fenoldopam has a rapid onset (4 minutes) and a short duration of action (<10 minutes) with intravenous administration,11 and has been reported to be an effective parenteral agent in severely hypertensive patients.9 The agent undergoes sulfate, methylate and glucuronide conjugation, and produces no accumulation of toxic metabolic or degradation products.12 Sodium nitroprusside (sodium nitroferricyanide) (NTP) has potent venodilating and arteriolar-dilating properties13 and in many respects is an ideal antihypertensive agent when rapid reduction of BP is required. NTP quickly and reliably reduces BP in most patients and its short half-life aids in rapid titration of the drug. One major drawback associated with the use of NTP is that the very potency that gives it utility has often led to restrictions on its use. Restrictions include invasive monitoring requirements or use in an intensive care setting, thus dramatically escalating the cost associated with NTPs use.14 A second drawback is that the formation of thiocyanate degradation products resulting in toxicity has limited its utility.14 While thiocyanate toxicity has been primarily associated with impaired renal or hepatic function, in which the typical 4-day half-life of thiocyanate is prolonged, reports of toxicity in patients with normal renal function have also occurred.14 Herein, we compared and evaluated the effects of sodium nitroprusside and intravenous fenoldopam mesylate in an open-label, randomized, multicenter trial of patients with severe systemic hypertension.

Drug-induced supraventricular tachycardia: A case report of fluoxetine

We report the occurrence of supraventricular tachycardia and hypotension in a 54-year-old woman after maintenance therapy with fluoxetine. Although cases of tachycardia and palpitations have been reported, supraventricular tachycardia and hypotension have not been directly attributed to fluoxetine.

Effects of hyperventilation on conjunctival oxygen tension in humans

A polarographic conjunctival oxygen sensor was used to measure oxygen tension in a tissue bed supplied by the internal carotid artery. The shared vascular source of the conjunctiva and brain suggests that conjunctival PO2 monitoring may provide an index of cerebral perfusion. We studied the effects of hyperventilation, a known stimulus of cerebral vasoconstriction, on conjunctival oxygen tension (PcjO2) in six normal, healthy adults; arterial blood gases were simultaneously measured in four of these subjects. A 5-min period of hyperventilation to a PaCO2 near 20 torr resulted in a rapid and significant (p less than .01) increase in systemic oxygen tension as measured by arterial blood gases and a transcutaneous oxygen monitor. These values gradually returned to baseline upon cessation of hyperventilation. PcjO2, however, decreased significantly (p less than .01) during hyperventilation, suggesting vasoconstriction of the conjunctival vascular supply. Because these changes temporally correlate with the cerebral vasoconstriction during hyperventilation, the conjunctival index of tissue oxygen tension may correlate with cerebral perfusion.

Prediction of changing cerebral blood flow by use of the conjunctival oxygen tension/arterial oxygen tension index

Current methods of assessing cerebral blood flow (CBF) are limited in their ability to provide data at the bedside in a timely, inexpensive, and continuous fashion. Since the palpebral conjunctiva is perfused by branches of the internal carotid artery, perfusion of this tissue may reflect global CBF. Conjunctival oxygen tension (Pcjo2). Pao2, Paco2, and pH were measured in ten healthy subjects during normal ventilation and active hyperventilation. CBF was measured simultaneously using positron emission tomography. CBF decreased from an average of 64.3 ± 15.1 ml × 100 g−1 × min−1 during baseline measurements to 33.2 ± 8.4 ml × 100 g−1 × min−1 during hyperventilation. The ratio of Pcjo2 to Pao2 (the Pcjo2/Pao2 index) decreased from 0.53 ± 0.07 to 0.35 ± 0.09 in the same time period. The Pcjo2/Pao2 index was significantly correlated with CBF (r = .78, p < .001). We conclude that the Pcjo2/Pao2 index may reflect the reduction in CBF induced by hyperventilation in normal humans, and should be investigated further as a method of assessing CBF in other settings which can result in globally reduced cerebral perfusion.

Deterioration of conjunctival PO2after CPR

An 82-year-old man was resuscitated following cardiac arrest suffered outside the hospital. Conjunctival oxygenation (PcjO 2 ), as measured by a conjunctival P0 2 monitor, increased in the immediate post-resuscitation period (60 min) and neurologic status improved. The PcjO 2 steadily declined over the next three hours. During the period of declining PcjO 2 , the systolic blood pressure tended to remain stable (104 mm Hg ± 18), the arterial PO 2 (PaO 2 ) was ⩾ 103 mm Hg, and the PcjO 2 /PaO 2 ratio initially increased, while the PcjO 2 /arterial oxygen content (CaO 2 ) ratio and neurologic status declined. The rise and subsequent fall of PcjO 2 in this patient paralleled the neurologic status and may be consistent with the cerebral reperfusion/hypoperfusion phenomena observed in experimental preparations of resuscitation from circulatory arrest.