Bombay Hospital Journal

Home > Table of Contents > Case Reports

Case Reports

Successful Use of Phosphodiesterase Inhibitors with High Dose Sympathomimetics in Cases of Refractory Cardiogenic Shock of Dilated Cardiomyopathy
Praveen P Jadhav*, Vivek G Patwardhan**, Deodatta Chaphekar***

Refractory cardiac failure complicated by shock and renal failure has a high mortality.1 The choies of treatment in this condition are restricted a secondary care setup. Here, we report two cases of idiopathic dilated cadiomyopathy, which presented with cardiogenic shock. The shock did not respond to usual doses of digitalis, dopaminergic agents and intensive monitoring. It was further complicated by multi-organ failure. The role of phosphodiesterase inhibitors in this situation is controversial due to its propensity to cause further hypotension and arrhythmogenesis. Though intra aortic balloon pump is an option, it may not be available in all setups. Hence we used increasing doses of pressor agents along with amrinone or milrinone. Here, we present report of two patients who responded dramatically to this therapy with return of blood pressure to normal and reversal of multi organ fialure.

Introduction

Treatment modalities for refractory heart failure are limited in a secondary care setup. The differences and problems of managing heart failure in India compared to that in the West (or a tertiary care center) have been ably pointed out.2 Phosphodiesterase inhibitors are not routinely recommended in patients with hypotension.3 This report suggests that addition of amrinone or milrinone to high dose dopamine and vasopressors may be a useful step in managing refractory heart failure complicated by shock and multi-organ failure.

Case Report

Fifty year old patient was brought with an episode of tonic posturing and up rollig of eyeballs, which was preceded by increasing dyspnoea on exertion of three days duration. He had episodic fever with chills and rigors for three days prior to admission. This fever was diagnosed to be due to plasmodium vivax malaria and treatment with chloroquine had been initiated the previous day. He was a known case of dilated cardiomyopathy, diagnosed two years ago, when he was admitted for congestive heart failure and arrhythmias at that time. Since then, he was on regular treatment with lanoxin, nitrates, low dose aspirin, low dose carvedilol, and intermittent courses of amiodarone. On admission, he had irregular pulse of 100 beats/minute, systolic blood pressure of 50 mmHg, sweating, cold clammy extremities, basal rales, third heart sound and hepatomegaly. His ejection fraction on 2 D Echocardiography was 10%.

He was started on dopamine drip at the rate of 12 mcg/kg/min and gradually increased to 30 mcg/kg/min. Except for transient rise of systolic BP to 70 mmHg, his BP did not rise beyond 60 mmHg in the next 12 hours. Hence, dobutamine at the rate of 15 mcg/kg/min and mephentermine at the rate of 1 mg intravenous (IV) and 1 mg every 4 hours intramuscular (IM) were added. This raised the systolic blood pressure to around 70 mmHg. The use of these agents beyond this dose was impossible due to side effects such as vomiting and ventricular arrhythmias. Multifocal ventricular beats were treated with amiodarone, 300 mg bolus over 2 hours, followed by 2 mg/min. The patient continued to have episodes of sweating and evidences of organ hypo perfusion in the form of irritability, raised liver enzymes and the most worrisome being severe oliguria. His urine output in the first 12 hours was zero and in the next 24 hours was 10 ml. The rising levels of renal parameters were presumed to be due to persistent hypotension as the patient had no prior history of renal problems, and urea levels at previous admission were normal. Nephrology consultant suggested the patient to be haemodialysed with a very high risk. The relatives were unwilling to take the risk and hence we were left with very little choices. He was started on amrinone with the loading dose of 0.5 mg/kg followed by an infusion rate of 6 mcg/kg/min. Lower doses were used in view of hypotension, liver and renal failure. Within 6 hours of starting amrinone, the patients’ systolic blood pressure reached between 90 and 100 mgHg and he started producing urine at the rate of 10 ml/hour. Each time his systolic BP reached beyond 100 mmHg, he was given 10 mg furosemide at hourly intervals. The requirement of furosemide was of 40 mg on the first day of amrinone therapy, 120 mg on the second day, 680 mg on the third day and 40 mg/2 hours on the fourth day. The urine output gradually increased and came to an acceptable level on the fifth day. Throughout the infusion of amrinone, patient was also receiving high dose sympathomimetics and vasopressors (dopamine at the rate 30 mcg/min, doubutamine at the rate of 30 mcg/kg/min and mephentermine at the rate of 1 mg every 4 hours). Once systolic blood pressure stabilized to 110 mmHg, this drip was tapered off under blood pressure and central venous pressure monitoring and dopamine at the renal dose was maintained. Blood pressure and evidences of organ hypo perfusion gradually improved over the next 7 days. Further course in the hospital was complicated by nosocomial chest infection, urinary infection and drug fever. However, patient overcame these complications with serial antibiotics (including antifungal agents). Eventually antibiotics were withdrawn in spite of persistent fever, presuming it to be drug fever. He was discharged from the hospital on 30th day with blood pressure of 130/90 mmHg, normal renal and hepatic parameters and left ventricular ejection fraction of 20%.

Investigations (partial) : (Table 1)

Case 2

Fifty-eight year old patient was brought with a four-day history of increasing dyspnoea on exertion, which led to severe breathlessness at rest since few hours prior to admission. The patient had completed a four hour air travel after taking discharge against medical advise from a medical centre in a foreign country four days earlier, where he was admitted for similar complaints. He was a known case of dilated cardiomyopathy diagnosed 10 years ago. He had clean coronary arteries on angiography. Since then, he was on regular treatment with lanoxin, nitrates, low dose aspirin, and enalapril. On admission, he had irregular pulse of 100 beats/minute, systolic blood pressure of 60 mmHg, sweating, altered sensorium, cold clammy extremities, crepitations all over the echocardiography was 20%.

He was started on dopamine drip at the rate of 10 mcg/kg/min and gradually increased to 30 mcg/kg/min. Since the blood pressure did not rise beyond 60 mmHg in the next 12 hours, dobutamine at the rate of 15 mcg/kg/min. Mephentermine at the rate of 1 mg IV and 1 mg every four hours IM were added. This raised the systolic blood pressure to around 70 mmHg. Beyond this dose, side effects such as vomiting and ventricular arrhythmias occurred. Multifocal ventricular beats were treated with amiodarone, 300 mg, bolus over 2 hours, followed by 2 mg/min. The patient continued to have episodes of sweating and evidences of organ hypo perfusion. He was started on milrinone with the loading dose of 50 mcg/kg over 10 minutes followed by an infusion rate of 0.5 mcg/kg/min. The patient deteriorated further with severe breathlessness, absent peripheral pulses and severe irritability due to cerebal anoxia. He had to be intubated and put on positive end expiratory pressure ventilation (PEEP). Tracheostomy was performed to aid ventilation. Respiration had to be paralysed with curare and he had to be continuously sedated to suppress irritability. Positive inotropic agents with milrinone was continued throughout this period. This gradually increased his blood pressure over the next 8-10 hours. Each time his systolic BP reached beyond 100 mgHg, he was given 10 mg furosemide. PEEP had to be continued for 24 hours. Urine output gradually improved over the next four days. Tracheostomy was weaned over next eight days. Once systolic blood pressure stabilized to 100 mmHg, inotropic agents was tapered off. Dopamine at the renal dose was maintained for few days. His renal and hepatic parameters showed a similar trend as in the previous patient. He was discharged from the hospital on 30th day with blood pressure of 90-70 mmHg, normal renal and hepatic parameters and left ventricular ejection fraction of 20%

Table 1



Parameters	Day 1	Day 6	Day 8	Day 14	Day 22	Day 29



Haemoglobin mg%	12.5	12.3	12.2	9.5	9.0	9.0
Leucocytes/cu mm	11,200	17,200	21,200	16,800	13,200	11,300
BUN mg%	88.4	136.6	166.8	111.5	36.0	11.3
Sr Creatinine mg%	—	6.7	—	3.2	1.5	0.9
Potassium Meq/lit	2.8	4.0	3.8	5.3	3.5	—
Urine examination	Trace albumin	Puscells, Alb+++, candida	Albumin +++	Albumin +, candida	Normal	Normal

Discussion

These cases revealed two important points. It illustrates successful management of refractory and complicated heart failure in a secondary care setup where ideal and best of facilities may not be available. It has already been suggested that management of such situations may differ than that mentioned in Western textbooks.2

More importantly, we suggest an important modality of treatment when facilities such as intra aortic balloon pump and dialysis are not available or not affordable. Addition of amrinone or milrinone to high dose doapminergic agents and vasopressors may benefit patients with resistant and complicated heart failure. Dopamine, at high doses, has predominantly alpha and mild beta effects.3 Similarly mephentermine also has alpha and beta agonist effects at doses used.4 Apart from increasing cardiac contractility, this action may lead to splanchnic vasoconstriction and worsening of renal failure. Amrinone and milrinone are myocardial phosphodiesterase inhibitors which result in increased intacellular cyclic AMP production and thus increased myocardial contractility. They are also potent vasodilators by their direct effects on vascular smooth muscle.3 While the former effect may be useful in treatment of depressed myocardial contractility, the latter may be useful to counteract the deleterious effects of vasopressor agents. Due to its vasodilatory properties, phosphodiesterase inhibitors are not advocated in hypotensive states. However, these cases illustrate its usefulness in combination with high dose dopaminergic and adrenergic agents even in hypotensive state.

We suggest that further case reports are needed to validate this observation. It must be stressed that both these cases were patients of idiopathic dilated cardiomyopathy with normal coronary arteries. This therapy may not accure desired results in patients with ischaemic cardiomypathy due to complicating myocardial ischaemia. However, it can be tried in desperate situations of cardiogenic shock complicating ischaemic heart disease also. Once substantiated, it can become an important step in the management of complicated refractory heart failure.

References

1.	Knaus WA, Draper E, Wagner DP, Zimmerman JE. Prognosis in acute organ-system failure. Ann Surg 1985; 202 : 685.
2.	Hegde BM. Medical textbooks in India. J Assoc Physicians India 2000; 48 (6) : 631-4.
3.	Mithcello MA. Appendix: Drug Index. In: Marso SP, Griffin BP, Topol EJ, editors. Manual of cardiovascular medicine. Philadelphia: Lippincott, Williams and Wilkins; 2000 : pp 813.
4.	Satoskar RS, Bhandarkar SD. Adrenergic and adrenergic blocking drugs. In : Satoskar RS, Bhandarkar SD, editors. Pharmacology and Pharmacotherapeutics. 9th ed. Bombay: Popular Prakashan; 1985 : pp 215.

EVIDENCE ON STANDARD TREATMENT OF HEPATIC ENCEPHALOPATHY IS UNCERTAIN

Non-absorbable disaccharides (lactulose and lactitol) are considered the treatment of choice for hepatic encephalopathy, but evidence neither supports nor refutes their use. Analysing 22 trials including 898 patients with hepatic encephalopathy, Als-Nielsen and colleagues found that patients taking lactulose and lactilol had the same mortality, but lower blood ammonia concentrations, than those who took placebo or had no intervention. They were more likely to show no improvement than those taking antibiotics, but whether this difference is clinically important is unclear.

BMJ, 2004; 328 : 1046.