Paradoxic, Glycerol-Trinitrate Induced Hypertension

Abstract

To the Editor: Nitrates are used intravenously for various indications. When given intravenously, they rapidly reduce BP, and since they have a short half-life they are excellent agents for the urgent treatment of excessive hypertension especially in patients with ischemic heart disease and congestive heart failure.1Cottrell JE Turndorf H Intravenous nitroglycerin.Am Heart J. 1978; 96: 550-553Abstract Full Text PDF PubMed Scopus (34) Google Scholar We report a case in which intravenous (IV) glycerol-trinitrate ([GTN] Nitrocine, Sanol Schwartz, Monheim, Germany) paradoxically caused BP elevation. A 72-year-old woman with ischemic heart disease, hypertension, and recurrent pulmonary edema treated with enalapril, furosemide, and a low sodium diet, had been admitted for pulmonary edema secondary to myocardial ischemia which necessitated prompt intubation and mechanical ventilation. On the day of admission after a high salt meal and excessive effort, she developed pain and dyspnea. On admission BP was 210/120 mm Hg. Neurologic examination was normal and eye examination revealed slight narrowing of the retinal arteries. She was admitted to the ICU and IV administration of GTN was started at doses of 0.05 to 0.1 mg/min. Blood pressure was measured every 3 min by an automatic DINAMAP sphygmomanometer (Critioln, EL), and intra-arterially, and its values were reduced to 170/100 mm Hg and congestive heart failure improved. Twenty hours after admission, BP suddenly rose to values of 220/140 mm Hg, the IV GTN dose was gradually increased up to 0.4 mg min, but BP continued to rise up to 300/220 mm Hg. Actually, BP rose with every increment in the dose of the GTN, and indeed when reduced, BP went down to 240/170 mm Hg. The process was repeated and every time GTN dose was reduced, BP came down only to increase again when GTN dose was increased. As we could not explain this effect, we thought the medication might have been replaced by mistake, so a new GTN ampulla was started; nevertheless, as GTN was given BP rose again. We discontinued GTN. Nifedipin was given enterally and BP was controlled at level of 170/100 mm Hg. At that time, repeated neurologic and eye examination were unchanged. Five hours later, left hemiparesis had occurred. Over the next month, the patient gradually improved her strength, which returned to near normal, and BP was well controlled and remained so, over 1 year of follow-up. Urinary catecholamines were found to be normal. Two weeks after the stroke, IV GTN was given and this time, it caused reduction of BP. This case shows a paradoxical effect of GTN on BP in a patient with excessive hypertension and pulmonary edema. This effect was transient, occurred 20 hours after beginning of treatment, and was not reproducible 2 weeks later. We suggest that the special circumstances that caused this paradoxical effect were the first sign of the cerebrovascular accident that followed. In the setting of stroke, cerebral autoregulation may be impaired or lost and this may induce hypertension.2Mchenry Jr, LC West JW Cooper ES Goldberg HI Jaffe ME Cerebral autoregulation in man.Stroke. 1974; 5: 695-706Crossref PubMed Scopus (57) Google Scholar,3Phillips SJ Whisnant JP Hypertension and the brain.Arch Intern Med. 1992; 152: 938-945Crossref PubMed Scopus (125) Google Scholar Nitrates increase the cerebral blood flow and may further increase the intracranial pressure,4Garner L Sodium nitroprusside treatment in patients with acute strokes [letter].Arch Intern Med. 1986; 146: 1454Crossref PubMed Scopus (3) Google Scholar and when cerebral flow autoregulation was lost, GTN might have had aggravated the stroke induced hypertension. Alternative explanation may be that after 20 h of treatment, nitrate tolerance developed peripherally, while the increment in the cerebral blood flow was maintained and aggravated the stroke induced hypertension.