RHABDOMYOLYSIS-INDUCED ACUTE RENAL FAILURE AFTER

METHADONE-DIAZEPAM OVERDOSE(case report)

B.Pavlovski, L.Milosevska, A. Cibisev, D. Petrovski,F. Licoska, A. Babulovska

Clinic of Toxicology and Urgent Internal Medicine,UCC.Skopje, R. Macedonia

BACKGROUND

RHABDOMYOLYSIS – GENERAL VIEW

Rhabdomyolysis is a syndrome caused by injury to skeletal muscles and the resultant leakage of muscle cell contents (myoglobin, potassium, phosphate, etc.) into the plasma.

TOXIC CAUSES

RHABDOMYOLYSIS HAS BEEN ASSOCIATED WITH A VARIETY OF TOXINS AND DRUGS. THEY CAN EITHER EXERT A DIRECT TOXIC EFFECT ON MUSCLES (METABOLIC POISONS) OR INDIRECTLY PREDISPOSE TO RHABDOMYOLYSIS.

DIRECT TOXIC EFFECT: Amatoxins

Carbon monoxide

Colchicine

Ethylene glycol

Snakebite

INDIRECT EFFECT: EXCESSIVE MUSCULAR HYPERACTIVITY OR RIGIDITY

PROLONGED SEIZURES

HYPERTERMIA

MUSCULAR COMPRESSION FROM PROLONGED IMMOBILITY (COMA)

NON-TOXIC CAUSES

COMA OR PROLONGED IMMOBILITY FROM ANY CAUSE

DIRECT MUSCLE INJURY

ISCHAEMIC MUSCLE INJURY

CRUSH INJURY

VASCULAR OCCLUSION

• IN THIS STUDY WE AIMED TO DESCRIBE ONE CASE WHO DEVELOPED ACUTE RENAL FAILURE AFTER RECENT INTRAVENOUS METHADONE-DIAZEPAM ABUSE

• OBJECTIVE:• A 30-years old man, known to be a heroin addict, was found at work

place, totally unrousable, bent on his hips in the lotus position.• On admission (18.April, 2007), in General Hospital in Ohrid he was in

coma state with miosis and acute respiratory depression, respiratory failure requiring intubation and artificial ventilation

• AT THE RECEPTION AT OUR CLINIC, HE WAS STILL IN SOPOROUS STATE WITH MIOSIS AND HYPOTENSION AND PROLONGED IMMOBILITY

• ROUTINE BIOCHEMICAL TESTS WERE DETERMINED: Blood tests, serum transaminases,

• ALT, AST,GGT,AF,LDH,CPK,CRP, bilirubine,coagulation factors, proteins, lipids, electrolytes, urine, alkali-acid status and markers of Hepatitis A,B,C and HIV

Hourly, urine output were measured.Liver ECHO, RTG-Chest and the CT scan of the brain were made also.Urine concentrations of Opiates and Benzodiazepines were determined using TLC and EMIT technique.

RELEVANT INVESTIGATIONS

• A SERUM CREATINE PHOSPHOKINASE ACTIVITY GREATER THAN FIVE TIMES THE NORMAL VALUE (IN THE ABSENCE OF HEART AND BRAIN DISEASE) IS THE MOST SENSITIVE INDICATOR OF RHABDOMYOLYSIS

• MYOGLOBINAEMIA WAS THE REASON FOR A VISIBLE DISCOLORATION OF THE URINE (RED-BROWN).WE DID NOT HAVE A POSSIBILITY TO DO

A ORTHOTOLUIDINE REACTION (Hematest) to confirm the presence of myoglobinuria

• Kalaemia,calcaemia,phosphataemia,uricaemia,urea,serum creatinine,AST,ALT,LDH activities

THE MAIN CLINICAL FINDINGS:

INDURATION OF UPPER AND LOWER LIMB SUGGESTED RHABDOMYOLYSIS.

SKIN CNANGES DUE TO ISCHAEMIC TISSUE INJURY (DISCOLORATION, BLISTERS) WERE PRESENTED ON THE AFFECTED AREA.

DARK (RED-BROWN) URINE WAS A CLASSICAL MANIFESTATION OF RHABDOMYOLYSIS.

SIGNS RELATED TO COMPLICATIONS OF RHABDOMYOLYSIS – HYPERKALAEMIA, ACUTE RENAL FAILURE, METABOLIC ACIDOSIS WERE NOTED.

FOCAL POINTS IN THE TREATMENT:

• THE FIRST AIM OF TREATMENT WAS TO

SUPPORT VITAL FUNCTIONS

• CARDIO-PULMONARRY AND CEREBRAL

PHARMACOLOGICAL SUPPORT AND CONTROL

OF FLUIDS, ELECTROLYTES AND ALKALI-ACID

STATUS

• HAEMODIALYSIS

• Antibiotics,Vitamins,Corticosteroids,Infusions, Calcium

salts,Diuretics,Sodium Bicarbonate, were given

following laboratory findings.

RESULTS:

DURING THE TREATMENT IN THE INTENSIVE CARE UNIT SIX HAEMODIALYSIS WERE MADE

LABORATORY VALUES BEFORE THE STARTING DIALYTIC TREATMENT AND AFTER THE SIXTH HAEMODIALYSIS

CPK----------- 2764U/L--Last results -19.05.07---173U/L

Urea----------- 42,9mmol/L--------------------------- 9,7mmol/L

Creatinin----- 825micmol/L--------------------------86micmol/L

Na-------------- 136mmol/L-----------------------------140mmol/L

Potassium----- 5,0 mmol/L----------------------------4,8mmol/L

Ca -------------- 2,2 mmol/L----------------------------2,2mmol/L

AST-------------406U/L---------------------------------36U/L

ALT-------------439U/L--------------------------------47U/L

LDH-------------1353U/L-------------------------------586U/L

AF---------------73U/L----------------------------------120/U/L

LABORATORY FINDINGS

Hb—------------111— 94— 92---- 90-----90g/L

Er----------------3,7---- 3,0— 2,67--- 3,0-----3,0 (x10¹²/L)

Hct--------------0,30--- 0,27— 0,26------------0,28

Tr—-------------226---------- 257-------------277(x109/L)

Le----------------29,2---22,6----15,8- 13,6----8,0(x109/L)

Fe----------------13,0(ųmol/L)

TIBC----------- 39,8(ųmol/L)

BLOOD VALUES DURING THE TREATMENT AT THE CLINIC

URINE OUTPUT - diuresis

From 100 ml per day from 26 April.07, slowly increase to 6300 ml per day on 05 May. Last results from 19 May-1500ml per day

IN OUR DAILY TOXICOLOGICAL PRACTICE WE HAVE HAD MANY RHABDOMYOLYSIS AFTER HEROIN OVERDOSE AT HEROIN ADDICTS

DIALYTIC TREATMENT – NECESSARY AND

SUCCESSFUL IN CORRECTION

HYDROELECTROLYTIC IMBALANCE AND RENAL FUNCTION ALTERATIONS AND IT MAY BE A PATHOGENETIC THERAPY BY MYOGLOBIN REMOVAL FROM THE PLASMA

ALTHOUGHT RENAL RECOVERY WAS EXPECTED,

LONG –TERM IMMOBILITY CAUSED ONE POTENCIAL SERIOUS COMPLICATION AS

A DEEP PHLEBOTHROMBOSIS ON THE LEFT HAND AND THE LEFT LEG

THE PATIENT WILL CONTINUE WITH FURTHER TREATMENT WITH METHADONE MAINTENANCE THERAPY AND FRAHEPAN, LMWH, ( Low molecular weight heparin), AND REHABILITATION TREATMENT IN

“SVETI ERAZMO” HOSPITAL IN OHRID