Burns

1. Continue all usual meds except ACEi, which should be stopped 24hr prior.

2. Three glasses of water at home with 50mg crushed Captopril PO.

3. Do DTPA renography (^99mdiethylenetriaminepentaaacetate) 1hr later while replacing urinary losses.

4. Positive test is either: Peak activity >11min, or GFR ratio >1.5.) & check IVP to r/o renal stenosis.

Captopril Test: check plasma renin activity (PRA) while sitting, before and 1hr after 25-50mg crushed Captopril PO, + if baseline increases >150%. Avoid Na restriction before test. Also should have stimulated renin of 10-12 mcg/L/hr and incr in renin by 10ug/L/hr.).

Tx: Drugs used: Nitroprusside & NTG | Fenoldopam, Enalapril, Nicardipine, Cleviprex (Clevidipine) | Hydralazine, Labetalol, Phentolamine | Esmolol & Other IV Meds, Condition & Recc Tx |

Other: Pt need immediate admission to ICU for tx and evaluation. Encourage bed rest, quiet dark room. Minimize saline infusions.

Goal –> decr MAP (DBP + 1/3 pulse pressure (S-DBP)) 20-25% in 30-60min. The goal is to lower BP by 10-15% in the first few hours and not >25% in first 24h. Decr DBP to no less than 100mmHg, then SBP to no less than 160 (or MAP to no less than 120) in the 1^st 24hr. (To avoid decr blood flow to brain/ kidneys, heart).

Pearls: Also inquire about the pt’s concurrent antihypertensive tx’s and history. The longer a pt has HTN, the better they have adapted to high perfusion pressure, more likely to tolerate the high BP, yet more likely to have cerebral ischemia if pressure drops too fast. Elderly pt’s autoregulate poorly in the CNS, thus a rapid lowering of BP may precipitate ischemic cerebrovascular events. Volume depletion via pressure induced diuresis is present in many pt’s, thus orthostatic BP should be obtained to determine the volume status….diuretics should be avoided if volume depletion is present. In patients with hypertensive nephropathy (GFR 20-60 mL/min) and metabolic acidosis (venous total CO2 less than 22 mmol/L), alkali treatment (sodium citrate @1 meq/kg HCO3 equivalent daily in 3 divided doses) reduces tubulointerstitial injury and slows the decline in GFR a prospective study suggests (Kidney Int 2010;January 13 online)……The rate of estimated GFR decline was also significantly slower in the citrate group (-1.60 vs -3.79 mL/min per year, p < 0.0001).

Vasodilators:

DOC is IV Nitroprusside (Nitropress, Nipride): start @0.25-1ug/kg/min infusion, titrate up to 8ug/kg/min. It dilates both arteries and veins to decr preload & afterload. Onset in 1-2min, DOA 1-10min after stop drip.

Risk: Thiocyanate toxicity (T-½ 4d in normal renal function) –> As contains an iron molecule coordinated to 5 cyanide molecules and one molecule of nitric oxide (endothelial derived relaxation factor). More common in poorly nourished and rapid infusions. Tx of cyanide toxicity consists of discontinuing nitroprusside, providing a buffer for cyanide by using sodium nitrite to convert as much hemoglobin into methemoglobin as the patient can safely tolerate; and then infusing sodium thiosulfate in sufficient quantity to convert the cyanide into thiocyanate. Consider Cyanide Antidote Kits

Teratogenic effects: Pregnancy Category C. Can cause sequestration of hemoglobin as methemoglobin.

S/s: anorexia, malaise, H-A, abd pain, MS changes, fatigue, sz, arrhythmia. May have a serum lactate level >10 mmol/L A clinical dx.

Tx: with Na-thiosulfate 12.5g IV. Can prevent with 5-10g thiosulfate IV qd or hydroxocobalamin. (Nitroprusside toxicity. Emerg Med 2000;10:71-75)

Contra: prolonged use in hepatic/renal insufficiency, azotemia, incr ICP.

Indicated for: CHF, aortic dissection (in combo with beta blocker) and catecholamine excess.

Begin concomitant long term tx –> start PO meds as soon as under control to reduce the risk of toxicity. Asses volume status. Reflex volume retention may occur after a few days on non diuretic drugs. Avoid Na restriction during the early phase of tx.

IV Nitroglycerine (NTG, Tridil): DOC if have coronary ischemia. Start @ 5-10mcg/min, titrate by 5-10 mcg/min q3-5min, if no response at 20 mcg/min, then titrate by 10 mcg/min (max 100-200 mcg/min or 0.1-4 mcg/kg/min). Onset in 2-5min, duration of 3-5min. Tolerance can occur in 24-48hr. Contra: CVA, avoid in HTN Encephalopathy as can increase ICP. Mix: 50 mg in 250 ml NS/D5W. Aerosol spray 0.4 mg/dose, 1-2 sprays sublingually; no more that 3 sprays in 15 minutes. Pt’s presenting to the emergency department with hypertensive and severely decompensated heart failure respond well to high-dose IV nitroglycerin (2 mg bolus, followed by a 20 mcg/minute infusion q3-5 minutes, with a max of ten doses)(mean total dose was 6.5 mg) (Ann Emerg Med 2007;50:144-152)…results in a lower risk of ICU admission (37.9% vs 80% of controls) and of endotracheal intubation (13.8% vs 26.7% in controls).

Fenoldopam (Corlopam): IV start @ 0.1 mcg/kg/min continuous infusion (no bolus), titrate in increments of 0.05-0.1 q15min until response or until 1.6 mcg/kg/min to avoid reflex tachy. Takes 4-5min to work,T-½ 5min by liver (loses 50% of its effect in 5min). Start PO meds anytime, taper or abruptly stop. A selective, peripheral DA₁ receptor agonist for short term use (up to 48hr) as get tolerance. Protects renal blood flow, inducing diuresis and natriuresis to hasten recovery.

Contra: glaucoma/ incr IOP. SE: H-A, dizzy, flushing, incr K. (NEJM 2001;345:21). Leads to increased renal blood flow has shown some promise to prevent contrast nephropathy in a few studies (Am J Card 2002;89:999-02 and Am Heart J 2002;143:894-03).

Enalaprilat (Vasotec): Start @ 0.625-1.25mg IV q6hr, can double dose q6hr to max of 5mg IV q6hr. If CC <30, then 0.626mg x1, may repeat in 1hr if inadequate response, then 1.25mg q6hr. Onset in 15-30min, lasts 6hr. First dose hypotension with volume depletion. Preserves cerebral blood flow when BP falls. Contra: severe renal insufficiency. Variable response.

Nicardipine (Cardene): 5-15mg/hr IV infusion. Onset 5-20min, lasts 1-2hr. 5 mg/hr (50 ml/hr), increase PRN q5-15 min 2.5 mg/hr, decrease dose to 3 mg/hr or 30 ml/hr when stable. A premixed formulation for nicardipine HCl IV injection will be available in 200-mL ready-to-use bags containing 20 mg (0.1 mg/mL) in either dextrose or sodium chloride and is intended to improve product convenience was FDA approved in 8/08. Previously was available in 25-mg ampules requiring dilution with 240 mL of compatible fluid (Mix 25 mg/10 ml ampule + 240 ml NS/D5W to equal 0.10 mg/ml). Indicated for the short-term treatment of hypertension when oral therapy is not feasible or desirable. Contra: AVB, CHF, angina.

Cleviprex (Clevidipine): start @ 1 to 2 mg/hour IV, titrate to 4 to 6 mg/hour. Ultra short-acting dihydropyridine calcium channel blocker and will be used when tight BP control and rapid titration are important. It has a much shorter duration than IV nicardipine…about 15 minutes for clevidipine compared to 5 hours for nicardipine. Not associated with bronchospasm or bradycardia like esmolol…and it doesn’t require a change in dose for renal or hepatic impairment. It costs around $180 per 25 mg vial. That’s MORE than esmolol and a little less than IV nicardipine. Avoid Cleviprex in patients allergic to eggs or soy since it contains these. A lipid emulsion containing about 2 kcal/mL. This may be important in patients on TPN or those with high triglycerides. Cleviprex is a milky-appearing lipid emulsion supplied in 50 mL and 100 mL glass vials containing 25 mg and 50 mg clevidipine, respectively (0.5 mg per mL). Each 1 mg to 2 mg per hour increase in dose will decrease systolic blood pressure by about 2 mm Hg to 4 mm Hg. Initially, the dose can be doubled every 90 seconds if needed. But as the blood pressure goal is approached, the time between dosage increases should be lengthened to five minutes to 10 minutes. No more than 1000 mL is recommended per 24 hours due to lipid load (i.e., 200 g per 1000 mL). Doses of up to 32 mg per hour have been used for a short time, but there is limited experience. Like esmolol, clevidipine’s quick onset and rapid metabolism by plasma esterases will also make it useful perioperatively and in the critical care setting. Clevidipine lacks esmolol’s risk of bronchospasm, and carries less risk of myocardial depression (Prescriber’s Letter 2008;15:10). Clevidipine infusion, starting at 2 mg/hour rapidly and safely reduced blood pressure in patients with severe acute hypertension, according to a report from investigators in the VELOCITY trial with 117 adults (Ann Emerg Med 2009;53:329-338)…..Within 30 minutes of starting clevidipine, 88.9% of patients achieved target blood pressures. Median time to target was 10.9 minutes. In 92.3% of patients, no other intravenous antihypertensive agents were needed. Clevidipine was well tolerated…..Transition to oral antihypertensive therapy within 6 hours after stopping the infusion was successful in 91.3% of patients. Half-life of approximately one minute.

SE: headache (6.3%), nausea (4.8%), and vomiting (3.2%). Acute renal failure (9%), atrial fibrillation (21%), and nausea (21%). No affect CYP450 enzymes and no drug interaction studies known.

Contra: patients allergic to soy or eggs. Patients with aortic stenosis or lipid metabolism defects. Pregnancy Category C.

Hydralazine (Apresoline): [10, 25, 50, 100 mg tabs. 1.25, 2, 4 mg/mL elixir. Injection: 20 mg/mL]

Hypertensive crisis: Adult @ 10–40 mg IM or IV Q4–6 hr PRN. Child @ 0.1–0.2 mg/kg/dose IM or IV Q4–6 hr PRN; max. dose: 20 mg/dose. Usual IV/IM dosage range is 1.7–3.5 mg/kg/24 hr.

Chronic HTN: Adult @ 10–50 mg/dose PO QID; max. dose: 300 mg/24 hr. Infant and child @ start at 0.75–1 mg/kg/24 hr PO divided Q6–12 hr (max. dose: 25 mg/dose). If necessary, increase dose over 3–4 wk up to a max. dose of 5 mg/kg/24 hr for infants and 7.5 mg/kg/24 hr for children; or 200 mg/24 hr.

Info: Use with caution in severe renal and cardiac disease. Slow acetylators, pt’s receiving high-dose chronic therapy, and those with renal insufficiency are at highest risk for lupus-like syndrome (generally reversible). May cause reflex tachycardia, palpitations, dizziness, headaches, and GI discomfort. MAO inhibitors and beta-blockers may increase hypotensive effects. Indomethacin may decrease hypotensive effects. Drug undergoes first pass metabolism. Onset of action: PO: 20–30 min; IV: 5–20 min. Duration of action: PO: 2–4 hr; IV: 2–6 hr. Adjust dose in renal failure. Good for eclampsia.

Contra: coronary insufficiency, aortic dissection, CVA.

Diazoxide (Hyperstat): [15 mg/mL IV, 50 mg/mL elixir] @1-3mg/kg (max 150mg) IV bolus q5-15min (give over 30 sec). Max dose of 150 mg/dose. Onset in 2-4min, DOA 3-12hr. Not used because you can not control the drop in bp response and profound sudden hypotension can be very serious.

Contra: coronary syndromes, CVA, dissecting aneurism or pulmonary edema, sulfa allergy. SE: nausea, flushing, tachy, hyperglycemia, fluid retention, aggravation of angina.

Adrenergic Inhibitors:

Labetalol (Normodyne, Trandate): good if signs of hyperadrenergic activity. @20mg IV over 2min, additional doses of 20-80mg q5-10min, then q3-4hr PRN (max 300mg IV) or 2mg/min infusion. Max effect in 30min, lasts 3-6hr. To convert to PO, give 200mg PO x1 when BP controlled, then 200-400mg PO q6-12hr.

Phentolamine (Regitine): Pheo’s @ 5-20 mg boluses every 5-10min. Onset in 1-2min, lasts 20min. Nitroprusside easier to use and is a better choice. Contra: syndromes of coronary insufficiency.

Esmolol (Brevibloc): 500ug/kg over 60sec, then 50ug/kg/min. Good estimate for loading dose = (pt’s wt in kg/2) = mg given over 1min, then X 0.1 = mg/kg/min drip rate. Onset 1-2min, lasts 15-30 min. Contra: AVB, CHF, severe broncho-constriction.

Other IV HTN Meds:

Atenolol (Tenormin, Atenil, Betatop): 5 mg IV over 5 min, repeat dose in 10 min. A beta-adrenergic blocker.

Propranolol: IV @ 1-10 mg load followed by 3 mg/hr or PO @ 80-640 mg daily. It has an immediate onset and lasts for 2 hrs for IV dose and 12 hours for the oral dose. The primary use of this medication is as an adjunct to potent vasodilators to prevent tachycardia. It does not usually lower BP acutely. A beta-adrenergic blocker.

Diltiazem (Cardizem): 0.25 mg/kg IV over 2 min, 2nd bolus in 15 min PRN 0.35 mg/kg. Infusion 5-15 mg/hr titrated HR. Mix: 25 ml (125 mg) in 100 ml D5W (1 mg/ml).

Verapamil (Isoptin, Calan): Antidysrhythmia 2.5-5 mg IV slowly, repeat PRN in 15-30 min 5-10 mg IV, max total 20 mg. Hypertension 2.5-10 mg IV or 0.05-0.2 mg/kg IV.

Methyldopate (Aldomet): 250-500 mg (diluted) IV q6-8h, max dose 1 gm q6h.

Trimethaphan camsylate (Arfonad): 0.5-15 mg/min. A powerful ganglionic blocking agent, a direct arterial vasodilator and an alpha-adrenoceptor antagonist that acts to both decrease BP and reduce the force of myocardial contraction. It has the unfortunate side effects of orthostatic hypotension, abd ileus with vomiting, urinary retention, and blurred vision secondary to pupillary dilatation. Trimethaphan has fallen out of favor and is rarely used as a result of such side effects. Urinary Retention, Avoid in pregnancy. Onset in 1-5 minutes and lasts for 10 minutes. Used in pt’s with emergent tx of aortic dissection.

Clevidipine (Cleviprex): An investigational new calcium channel blocker with an ultrashort half-life. Clevidipine has shown promise in a study in pt’s presenting to the emergency room with an episode of severe acute hypertension (Chest 2007;132:477S).

Type of Condition: 1^st line drugs > 2^nd line:

Acute Aortic Dissection: Labetalol + nitroprusside. Esmolol > Nitroprusside > Propranolol > Tremthaphan.

Acute Coronary Syndrome / AMI: Nitroglycerin + beta-blocker. Nitroglycerin > Esmolol > Nitroprusside or Labetolol.

Pulmonary Edema or CHF: Nitroglycerin + Lasix. Nitroglycerine or Nitroprusside > Enalaprilat.

Acute Renal Failure: Fenoldopam or Nitroglycerine > Nicardapine. Multiple such as labetalol, hydralazine, beta-blocker, calcium channel blocker, clonidine, and fenoldopam.

Post-op HTN: Nitroprusside, Nitroglycerine, Fenoldopam > Labetolol.

Pheochromocytoma or Cocaine Intoxication: Phentolamine > Labetolol.

Rebound HTN: Restart the discontinued drug > Labetolol.

HTN Encephalopathy: Nitroprusside or Fenoldopam > Nitroglycerine. Multiple such as labetalol, hydralazine, beta-blocker, calcium channel blocker, clonidine, and fenoldopam.

Subarachnoid Hemorrhage: Labetalol or Nicardapine or Nimodipine > Nitroprusside.

Intracerebral Hematoma: Nitroprusside or Labetolol.

Ischemic stroke: Reassess need for therapy. Labetolol or Enalaprilat.

Pregnancy / preeclampsia: Labetolol > Hydralazine > Nifedipine of Nitroprusside.

Opoioid Withdrawal: Clonidine.

Microangiopathic hemolytic anemia: Multiple such as labetalol, hydralazine, beta-blocker, calcium channel blocker, clonidine, and fenoldopam.

Ddx: Diseases that Mimic HTN Emergency:

Acute LV failure, Uremia, CVA, SAH, brain tumor, head injury, epilepsy (post ictal), CVD with cerebral vasculitis, Encephalitis, Drug ingestion (sympathomimetics, PCP), Acute Intermittent Porphyria, incr Ca, Acute anxiety with hyperventilation syndrome. See secondary causes of HTN.

Ref: (Emergency room management of HTN urgencies and emergencies. J Clin Hyperten 2001;3:3) (Zachariah PK, Sheps SG. Chapter 60: Cardiovascular manifestations of HTN. A. Diagnosis. pages 1776-1798 (page 1778). IN: Giuliani ER, Gersh BJ, et al. Mayo Clinic Practice of Cardiology, Third Edition. Mosby. 1996)