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HYPERTENSION IN THE INPATIENT SETTING Mechanisms and Pharmacologic Management Dedicated to the memory of LEON I. GOLDBERG, MD, PHD A pioneer in the research of dopamine receptor pharmacology and physiology Learning Objectives Outline the prevalence, pathology, and pathophysiology of hypertension in the inpatient setting. Identify treatment goals and treatment options for the severely hypertensive patient. Discuss the pharmacologic profile and potential benefits of fenoldopam in the treatment of hypertension. Situations Requiring Inpatient Antihypertensive Treatment Preexisting Hypertension Primary / Essential Secondary No Preexisting Hypertension Acute Crisis Perioperative At least 45% of hospitalized patients have preexisting hypertension About 25% of surgical patients have preexisting hypertension Hypertensive patients frequently have coexisting cardiac and vascular disease Goldman L, et al. N Engl J Med 1977;297:845-850 Epidemiology and Relevance EM MICU SICU OR PACU Obstetrics Suite Parenteral Treatment of Hypertension May be Required in . Uncontrolled or Malignant Hypertension Drug-Induced Hypertension cocaine, amphetamines drug withdrawal drug-drug interactions Endocrine Disorders Parenteral Treatment of Hypertension May be Required for Medical Emergencies Parenteral Treatment of Hypertension May Be Required During/After Perioperative Period Cardiac Surgery Major Vascular Surgery carotid endarterectomy aortic surgery Neurosurgery Head and Neck Surgery Renal Transplantation Major Trauma - Burns or Head Injury Factors in the Development of Acute Hypertension PACU Pain Anxiety Distended Bladder Hypervolemia Vasoconstriction ER/CC Myocardial Ischemia Hypercarbia/ Hypoxemia Reduced organ perfusion -Renal -Cerebral OR Vascular clamping (afterload) Hyperdynamic Myocardium Malignant Hyperthermia Diastolic Dysfunction Adverse Consequences of Uncontrolled Hypertension Postsurgical Hemorrhage Suture line disruption Aortic dissection End Organ Injury Myocardial ischemia Stroke Renal failure Pulmonary Edema Adrenergic ToneBaroreceptor Reflexes Volume/Pressure Renin/Angiotensin Preload Cardiac Output Blood Pressure Catecholamines Adrenal Gland CNS Veins Arteries Capacitance Resistance Sympathetic Nervous System Regulation of Blood Pressure Heart Kidney Afterload Renin-Angiotensin-Aldosterone Regulation of Blood Pressure Blood Pressure Kidney Vasoconstriction Angiotensin IRenin Substrate Angiotensin II Renin Sodium 50:285-292 Therapy Treat the underlying cause Provide adequate anesthesia/analgesia Administer antihypertensive medications Inpatient Hypertension: Therapeutic Considerations 50 million adults have high blood pressure 25% are unaware of this condition 72.6% are not well controlled at goal of 2.4) (ECG, chest pain) (Pulmonary) (edema, CXR, rales) Ellis D, et al. (abstract) No evidence of rebound effects Rapid disappearance of drug Administration before or after discontinuation of infusion Wide variety of drugs used Generally successful transfer to oral drugs Transition to Oral Medications Safety in Postoperative Hypertension Studies Summary of SKF Studies: Overview Number Patients 17 (23.5%) 126 (18.2%) 28 (10.7%) (% female) (pilot 8, large study 20) Mean Age (yrs) F 51.0 yrs F 62.8 8 years F 58.6 yrs Plc 47.4 yrs Nif 60 9 yrs SNP 61.6 yrs Design Randomized Randomized Randomized Double-blind Single-blind Single-blind Placebo-controlled Positive-control (Nifedipine i.v.) Positive-control (Nitroprusside) Entry Criteria Surgery with 24 hours CABG within 24 hours Surgery with 24 hours SBP 20% preop baseline MAP 105 mmHg for 5 minutes SBP 130 mmHg requiring IV therapy Baseline BP 121 (SBP) F 114.1 9.1 (MAP) F 143 3/81 2.8 F (mmHg) 125 (SBP) P 114.2 8.5 (MAP) Nifed 148 2.9/82 2.6 SNP Goldberg, et al. (General Surgery) Mathur, et al. (CABG) Hill, et al. (Cardiovascular) A Comparative Trial of Fenoldopam and Nifedipine in Postoperative Hypertension Prospective, randomized, single-blinded, multicenter controlled trial Patient Population 126 postsurgical CABG patients MAP 105 mmHg for 5 minutes Adequate sedation / analgesia Design Single-blind, drug randomization, dose titration Dosing (up to 24 hours) IV fenoldopam: 0.1 - 1.6 g/kg/min IV nifedipine: 0.6 - 1.25 mg/hr Mathur V, et al. Crit Care Med 1998;26(Suppl) (abstract) Nifedipine (n=63) Fenoldopam (n=59) 118 112 106 100 94 88 82 0 10 20 30 40 50 60 120 240 360 post 60 post 180 post 360 end infusion * * * * *p 15 mmHg) Mathur, et al. Pulmonary Vascular Hemodynamics Pulmonary vascular resistance (PVR) decreased significantly during fenoldopam but not during nifedipine treatment. Pulmonary artery pressures (PAP) did not change significantly during therapy with either drug. Mathur, et al. Filling Pressures and Cardiac Output Mathur, et al. Heart Rate nifedipine fenoldopam 6050403020100 110 100 90 80 70 60 Time (min) p = NS, fenoldopam vs. nifedipine Heart Rate ( bpm ) Mathur, et al. RBF During General Anesthesia With Induced Hypotension Aronson S, et al. J Cardiothorac Vasc Anesth 1991;5:29-32 (Results of Dog Studies) MAP 50-60 MAP 50-60 Aronson S, et al. Can J Anesth 1990;37(3):380-384 RBF During General Anesthesia RBF During Induced Hypotension 1. 2. Renal Blood Flow Renal Blood Flow Germann R, et al. Crit Care Med 1995;23:1560-1566 Figure 1: Values expressed as mean + SEM. Fenoldopam (solid squares), Placebo (open squares). P values for differences compared with placebo for mucosal pO2, 2% in Combined SKF and Neurex Fenoldopam IV Therapeutic Studies Fenoldopam: Preparation Ampules MUST BE DILUTED before infusion Diluted in: 0.9% Sodium Chloride Injection USP 5% Dextrose Injection USP mL of Concentrate (mg of drug) Added toFinal Concentration 4 mL (40 mg) 1000 mL 40 g/mL 2 mL (20 mg) 500 mL 40 g/mL 1 mL (10 mg) 250 mL 40 g/mL Fenoldopam: Dosage and Administration Dosing Recommendations Usual starting dose = 0.1 g/kg/min Rapid titratable blood pressure control Minimal increase in heart rate Higher starting dose recommended For more rapid onset of blood pressure control For greater magnitude of effect Fenoldopam: Dosage and Administration Fenoldopam should be administered by continuous intravenous infusion A bolus dose should not be used Initial dose should be titrated upward or downward, no more frequently than every 15 minutes Recommended increments for titration are 0.05 to 0.1 g/kg/min Use of infusion pump or syringe pump recommended Intraarterial hemodynamic monitoring at discretion of treating physician Table 1. Causes of Acute Renal Failure Acute tubular necrosis Ischemic Nephrotoxic Renal vascular injury Preexisting renal insufficiency Systemic disease with renal involvement Acute interstitial nephritis Acute glomerulonephritis Adapted from Sladen R, et al. Problems in Anesthesia 1997;9(3):314-331 Table 2. High-Risk Procedures and Events Cardiac surgery Vascular surgery Biliary tract and hepatic surgery Urogenital surgery Complicated obstetrics Major trauma Adapted from Sladen R, et al. Problems in Anesthesia 1997;9(3):314-331 Incidence of Acute Renal Failure: Perioperative Risk Factors Requiring Dialysis Chertow GM, et al. Circulation 1997;95:878-884 CR CL 60 Prior Heart Surgery IABP Valve NYHA IV NYHA IV PVD NYHA IV Valve Cardiomegaly 6.1%2.1% 2.1%0.9% YesNo YesNoYesNoYesNo YesNo YesNo YesNo YesNo YesNo YesNo 0.4% 1.3% 2.8% 9.5% 5.0%2.3%1.1% Considerations in Patient Selection for Fenoldopam When maintenance of renal function (GFR) and increase in RBF is desired Patients at high risk for renal ischemia Patient
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