ACUTE RENAL FAILURE IN SEVERE MALARIA Dr Saroj

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ACUTE RENAL FAILURE IN SEVERE MALARIA Dr Saroj K Mishra Dr Kishore C Mahanta

ACUTE RENAL FAILURE IN SEVERE MALARIA Dr Saroj K Mishra Dr Kishore C Mahanta Ispat General Hospital, Rourkela Orissa India

INTRODUCTION • Malaria is one of top 10 killer diseases in world • ARF

INTRODUCTION • Malaria is one of top 10 killer diseases in world • ARF occurs in <1% of pf malaria, but mortality up to 45% • Common in adults than children, recent trends- high incidence • Diagnosed when sr. creat. >3 mg/dl or urine output <400 ml/24 hrs • Renal involvement varies from mild proteinuria to severe azotemia • Malarial ARF is associated with CM, Jaundice, Anaemia, ARDS/Pulm. edema & Hypoglycaemia

INTRODUCTION Contd. Two different settingsa) ARF as a component of MOF – present at

INTRODUCTION Contd. Two different settingsa) ARF as a component of MOF – present at the time of admission, Often associated with poor prognosis. b) Present as a sole complication at a later stage of the course, when other complications subsided or treated, Often associated with recovery.

Pathology & Pathogenesis • In mild cases- not much change in renal parenchyma- may

Pathology & Pathogenesis • In mild cases- not much change in renal parenchyma- may be minimal tubular degeneration, mild renal parenchymal change & presence of vacuoles • In severe cases- Tubular degeneration with distal tubular necrosis, Proximal tubules are often loaded with malarial pigments, Hb granules may be seen in the tubular cells

Pathology & Pathogenesis 2 • Most patients have little or no proteinuria & urinary

Pathology & Pathogenesis 2 • Most patients have little or no proteinuria & urinary sediment contains occasional granular and hyaline cast but no RBC. • Absence of hypertension, Rapid resolution without residual impairment & predominant in adults rather than children with urinary findings suggests- ARF results from ATN & not glomerulonephritis

Pathology & Pathogenesis 3 • ARF- mediated thro’ several mechanisms 1. Effect of p.

Pathology & Pathogenesis 3 • ARF- mediated thro’ several mechanisms 1. Effect of p. RBC on microcirculation- knob like processes formation on surface of RBC which helps in anchoring the endothelium Cytoadherence- due to thrombospondin formation from vascular endothelium- specific to pf ( not in pv/pm) so ARF only in pf. Loss of deformability of p. RBC according to need of microcirculation- slugish circulation- renal ischemia

Pathology & Pathogenesis 4 2. Hypovolumia may occur due to Fever (hyperpyrexia), sweating, decreased

Pathology & Pathogenesis 4 2. Hypovolumia may occur due to Fever (hyperpyrexia), sweating, decreased intake of fluid, vomiting etc. 3. DIC 4. Increased plasma viscosity due to infection 5. Release of chemical mediators- TNF, cachectin, cytokines, interleukines etc causesvasoconstriction, increased vascular permiability, catecholamine release(SIADH ) hemoconcentrarion, shock & tubular necrosis 6. Hyperbilirubinaemia due to hemolysis, Black water fever in G 6 PD deficiency patients is also associated with ARF

CLINICAL FEATURES ARF in severe malaria is common in adults, rare in children Two

CLINICAL FEATURES ARF in severe malaria is common in adults, rare in children Two subsets of presentationsa. ARF as a component of multi organ failure present since admission- poor prognosis, associated with anemia, jaundice, hypoglycemia, acidosis or coma b. Present as a sole complication- appears at a later stage when other complications subsided/treated – prognosis is good

CLINICAL FEATURES 2 • Diagnosis suspected when urine output <400 ml/24 hrs & confirmed

CLINICAL FEATURES 2 • Diagnosis suspected when urine output <400 ml/24 hrs & confirmed when sr. creatinine >3 mg/dl in adults & >1. 5 mg/dl in children • Patient may be anuric, oliguric, with normal urination or polyuric • Oliguric phase varies from few days to wks • Prerenal azotemia presents with signs of dehydration • Prolonged anuria/oliguria – volume over load due to decrease salt & water excretion

CLINICAL FEATURES 3 • Differentiation of prerenal & established ARF is important for management-

CLINICAL FEATURES 3 • Differentiation of prerenal & established ARF is important for management- sp. gr. of urine is >1. 020 & <1. 010 respectively • Vulnerable group of patientsa) Pregnant women, b) high parasitemia, c) very high jaundice d) prolonged dehydration e) on NSAID therapy • Patients with pfr +ve to be screened for ARF

CRITICAL DETERMINANTS • • Hypo & hyper volumia Hyperparasitemia Hemoconcentration Hyperbilirubinemia Hyperpyrexia Hyperkalemia Hyponatremia

CRITICAL DETERMINANTS • • Hypo & hyper volumia Hyperparasitemia Hemoconcentration Hyperbilirubinemia Hyperpyrexia Hyperkalemia Hyponatremia

LAB. INVESTIGATIONS & MONITORING • Peripheral smear for diagnosis & parasite clearance • Blood

LAB. INVESTIGATIONS & MONITORING • Peripheral smear for diagnosis & parasite clearance • Blood urea, creat. , bilirubin, SGPT, Na, K, HCO 3, PH • Urine sp. Gr. • ECG & chest X-ray when indicated

TREATMENT (Guidelines) • • Appropriate antimalarial at the earliest Maintenance of fluid & electrolytes

TREATMENT (Guidelines) • • Appropriate antimalarial at the earliest Maintenance of fluid & electrolytes Recording of intake output chart Prevention of fluid overload & secondary infection including pneumonia • Treatment of acquired infection at the earliest keeping an open mind

TREATMENT 2 • Meticulous record of fluid requirementfluid intake, urine output –guides the administration

TREATMENT 2 • Meticulous record of fluid requirementfluid intake, urine output –guides the administration of fluid, monitoring the improvement & most of all preventing fluid overload – a CVP line can be established • Daily sr creat estimation in severe pf malaria cases if possible

TREATMENT 3 • If the 24 hr urine output is <400 ml & the

TREATMENT 3 • If the 24 hr urine output is <400 ml & the patient is clinically dehydrated. Fluid challenge – 20 ml/kg of Normal saline over one hr. Monitor fluid overload after each 200 ml by- Chest auscultation, JVP, CVP at 0 & +5 Urine output should be 20 ml/hour

TREATMENT 4 • If no urine after fluid therapy. Diuretic challenge: Iv loop diuretic-

TREATMENT 4 • If no urine after fluid therapy. Diuretic challenge: Iv loop diuretic- Inj Furosemide in incremental dose 40 -100 -200 -400 mg at ½ hour interval • If no improvement. Dopamine challenge: Inj dopamine slow iv infusion at 2. 5 to 5 mcg/kg/min

RESPONSE • 75%of oliguric & 5%of anuric responds with increased urine output • No

RESPONSE • 75%of oliguric & 5%of anuric responds with increased urine output • No improvement in sr creat level • False sense of improvement • Reduces the risk of volume overload • If ineffective further fluid is restricted

CAUTION • • No benefit in oliguric patients No recovery in anuric patients Delay

CAUTION • • No benefit in oliguric patients No recovery in anuric patients Delay in decision for dialysis Complications of Dopamine- Gangrene, Ototoxicity

CAUTION 2 Avoid Nephrotoxic drug in ARF suspects • ACE inhibitors & cyclooxygenase inhibitors

CAUTION 2 Avoid Nephrotoxic drug in ARF suspects • ACE inhibitors & cyclooxygenase inhibitors (NSAIDs)- precipitate prerenal azotemia to ischemic ARF • Cephalosporines & Aminoglycosides • Assesment of renal function using urine output is dangerous in patients receiving Diuretics

Antimalarial Drugs • • - Qunine Can be given safely in pregnancy & ARF

Antimalarial Drugs • • - Qunine Can be given safely in pregnancy & ARF Initial dose of qunine -10 mg/kg 8 hrly Reduction after 48 hrs No dose adjustment during HD Artemisinine No modification is required in ARF

Indications for Dialysis Clinical : • Uraemic symptoms- Nausea, Vomiting, Hiccough, Flapping tremors, Muscle

Indications for Dialysis Clinical : • Uraemic symptoms- Nausea, Vomiting, Hiccough, Flapping tremors, Muscle twitching, & Convulsion • Fluid overload • Pericardial rub • Arrhythmia Laboratory: Rising creatinine, Hyperkalemia, (K >6. 5), Acidosis(HCO 3 <15 meq/l)

Haemodialysis • Advantages - Efficient method • Disadvantages - Only in selected centers -

Haemodialysis • Advantages - Efficient method • Disadvantages - Only in selected centers - Expertise - Lag time

Caution for conservative management of ARF in severe malaria • May develop critical signs

Caution for conservative management of ARF in severe malaria • May develop critical signs at any odd hrs without giving a scope for dialysis • Many patients have been lost as dialysis is decided but institution is delayed • Sudden cardiac death may ensue in a patient who is improving due to pulmonary edema or hyperkalaemia

PROGNOSIS • Mortality among renal failure is 45% to 10% those without • Death

PROGNOSIS • Mortality among renal failure is 45% to 10% those without • Death increases 3 fold in presence of ARF • Very high mortality in presence of MOF • Mortality can be reduced to 10% if early & frequent Dialysis is instituted • Survival with PD is lower than HD