JOURNAL OF EVIDENCE BASED MEDICINE AND HEALTHCARE

Table of Contents

2018 Month : May Volume : 5 Issue : 20 Page : 1571-1576

VENTRICULAR TACHYARRHYTHMIA IN FALCIPARUM MALARIA

Sunil Kumar Sharma1, Pradeep Kumar Mohanty2, Bhabagrahi Rath3, Suresh Chandra Sahoo4

1. Associate Professor, Department of Cardiology, Veer Surendra Sai Institute of Higher Medical Science and Research, (VSSIMSAR), Burla.
2. Associate Professor, Department of General Medicine, Veer Surendra Sai Institute of Higher Medical Science and Research, (VSSIMSAR), Burla.
3. Associate Professor, Department of Pharmacology, Veer Surendra Sai Institute of Higher Medical Science and Research, (VSSIMSAR), Burla.
4. Professor and Head, Department of Cardiology, Veer Surendra Sai Institute of Higher Medical Science and Research, (VSSIMSAR), Burla.

Corresponding Author:
Dr. Pradeep Kumar Mohanty,
Department of General Medicine,
Veer Surendra Sai Institute of Higher
Medical Science and Research, (VSSIMSAR), Burla.
E-mail: drpradepmohanty@rediffmail.com
DOI: 10.18410/jebmh/2018/331

ABSTRACT
BACKGROUND
Cinchona alkaloids Quinidine, Quinine commonly used as anti-malarial are able to suppress ionic conductance through K+ Na+ Ca++ channels in the membranes of a variety of different cells, blocking of outward membrane repolarising K+ current by quinidine can produce EADs and triggered rhythm in presence of low extracellular potassium. Hypokalaemia can occur early in treatment of malaria and is associated with prolonged repolarization. Hence presence of these two substrates can precipitate ventricular tachyarrhythmia in malaria.
The objectives of the study were to evaluate the occurrence of ventricular tachyarrhythmia and whether administration of quinine in dextrose solution is the precipitating factor for development of tachyarrhythmia by precipitating hypokalaemia.

MATERIALS AND METHODS
Present study was conducted in VSS Medical College now VSSIMASR Burla, Sambalpur, Odisha from June 1997 to Dec 2017. Severe falciparum malaria patients in the age group of 5 yrs. to more 70 years patient receiving quinine in dextrose solution and Artesunate IV or IM were observed for development of any sudden cardiac death, survivor cardiac arrest or VT. Serum potassium concentration and Q-Tc interval was measured in all cases.

RESULTS
234 cases of sudden cardiac death, survivor of cardiac arrest and VT were observed in patients receiving IV quinine but no event with Inj. Artesunate. Hypokalaemia and long Q-Tc was observed in all the cases developing ventricular tachyarrhythmia. Arrhythmia improved with rapid correction of potassium.

CONCLUSION
Current practice of administration of quinine in dextrose solution predisposes severe malaria to develop hypokalaemia. Hypokalaemia by prolonging repolarization predispose makes malaria patients susceptible to develop ventricular tachyarrhythmia in presence quinine. Hence quinine should not be used with dextrose solution and if it is essential to use, then early recognition and correction of hypokalaemia is essential to prevent ventricular tachyarrhythmia.

KEYWORDS
Severe malaria, Quinine, Hypokalaemia, Ventricular tachyarrhythmia.

How to cite this article

Sharma SK, Mohanty PK, Rath B, et al. Ventricular tachyarrhythmia in falciparum malaria. J. Evid. Based Med. Healthc. 2018; 5(20), 1571-1576. DOI: 10.18410/jebmh/2018/331

BACKGROUND

Severe malaria is a medical emergency requiring immediate administration of rapidly effective antimalarial drugs. In the largest randomised trials ever conducted in severe malaria, the artemisinin derivative artesunate proved to be markedly superior to quinine in the parenteral treatment of severe malaria and is therefore now the treatment of choice for all patients.1,2 But Cinchona alkaloid Quinine and Quinidine has been the mainstay of antimalarial treatment of severe malaria for last several years but has now been overtaken by the artemisinin derivatives. Nevertheless, quinine is still widely available and extensively used, and it needs to be kept available in case artemisinin resistance worsens. According National drug policy for malaria 2013 either of Artesunate IV or IM Artemether IM or Quinine IV Infusion should be used irrespective of Chloroquine resistance status of the area.3 Quinine is preferred over more potent quinidine as antimalarial because Quinine rarely cause cardiac complications and QT prolongation is mild unless there is Acute overdose.4

There is abundant evidence that quinine and quinidine are able to suppress ionic conductance through K+ Na+ Ca++ channels in the membranes of a variety of different cell types5,6,7,8,9,10 Blocking effect of quinidine on the outward membrane repolarising K+ current results in prolongation of the action potential which can cause Early after depolarizations (EADs) and triggered activity particularly when the extracellular K+ concentration is low.11

Even though not widely reported hypokalaemia can develop early during treatment of severe malaria because of GI manifestation, poor oral intake, quinine induced insulin secretion and IV dextrose administration to avoid hypoglycaemia. Hypokalaemia alone can cause prolongation of ventricular repolarisation by inhibition of outward potassium currents and often associated with increased propensity for early after depolarizations. In addition, shortened refractoriness and slowed conduction contribute to reduced excitation wavelength thereby facilitating re-entry. Thus, hypokalaemia by causing prolongation of ventricular depolarization sets the stage for occurrence of arrhythmia in malaria receiving quinine group of drugs which are known to induce EADs and triggered rhythm.

During the resurgence of falciparum malaria in early 90s with severe pernicious manifestation and emergence of chloroquine resistance IV quinine was frequently used and we encountered many cases of sudden death and ventricular.  Tachycardia after wide availability of the artemisinin derivative artesunate in the first and second decade of 2000, the incidence of ventricular tachyarrhythmia has diminished raising the possibility that intravenous quinine in dextrose solution was probably responsible for occurrence of ventricular tachyarrhythmia in severe malaria.

 

Aims and Objectives-

This study was undertaken in our medical college hospital to find the reason for occurrence of tachyarrhythmia in falciparum malaria receiving quinine but not with the artemisinin derivative artesunate and suggest remedial measure to decrease the incidence of ventricular tachyarrhythmia.

 

MATERIALS AND METHODS

Present study was conducted in VSS Medical College now VSSIMASR Burla, Sambalpur, Odisha from June 1997 to Dec 2017. Data were also collected from nearby private hospital and clinical establishment with special reference to report occurrence of sudden death, ventricular tachyarrhythmia observed by them. As our institute is the only centre having dept. of Cardiology almost all the cases are referred here for further evaluation and treatment or the concerned physician take our opinion regarding such arrhythmia during treatment of severe malaria. Equal number of sick malaria patients receiving artesunate not manifesting with arrhythmia were included for any baseline ECG abnormality and electrolyte concentration as artesunate does not cause any significant cardiovascular abnormality.12

 

All the data are collected and stored for review by the faculties of dept. of cardiology. As this dept. caters to 24 hours emergency we get the opportunity to record all events occurring even in emergency hours so that we do not miss any events. Patients of all age groups from 5 years to more than 70 yrs and sex were analysed. Special care was taken to exclude patient with underlying heart disease, CKD or patient taking diuretic for any other indication which may influence interpretation.

Electrolytes were estimated by ISE (Ion selective electrode) method with fully automatic electrolyte analyser with special reference to sodium and potassium concentration. Calcium Magnesium concentration were also measured. Hyponatraemia was defined when Na concentration is less than 135 meq/L (135 mmol/L) with severe hyponatraemia less than 110 meq/l, hypernatraemia >145 meq/L. Hypokalaemia was defined by serum potassium less than 3.5 meq/L (3.5 mmol/l) hyperkalaemia when serum potassium >5.0 meq/L (5.0 mmol/L). Normal total plasma calcium concentration is 8.5 -10.5 mg/l (2.1-2.6 mmol/l) hypocalcaemia when serum calcium less than 8.5 mg/l (ionized calcium <4.6 mg/l (2.1 mmol/L and 1.15 mmol/L). hypercalcemia >10.5 mg/l (2.6 mmol/L). Normal magnesium concentration is 1.8-3.0 mg/l (0.75-1.25 mmol/l).13

12 lead ECG were done in all the cases. 12 lead ECG was analysed by two independent observers with special reference to calculate the PR interval QRS duration ST segment, QT interval and presence of U wave. The following features in ECG was searched for presence of hypokalaemia: flattening or inversion of T wave, Q-T interval prolongation (longer duration of the T wave), visible U wave, mild ST depression (0.5 mm), ventricular extrasystoles. Special reference was given to measure Q-Tc adopting the Bazzets formula14 QTC = QT / √ RR; manually with the help of mathematical calculator and automated ECG machine. The normal value for QTC is 0.39 sec ± 0.04 sec (0.35 to 0.43 sec). Patient were monitored continuously if patients were complaining of transient disorientation or acute SOB with suspicion of arrhythmia to detect any VPCS, NSVT, VT during observation period. VT was defined as salvos of more than consecutive bizarre premature complexes at rate more than 100 / min and lasting for 30 secs or more Torsades de pointes was recognised as polymorphic tachycardia characterized by QRS peaks that seem to twist around the baseline.15

Routine echocardiography was done in all cases who survived Cardiac arrest or VT to exclude underlying structural heart disease.

Pt having underlying LV dysfunction or valvular lesion were excluded from study is it may influence analysis. Case records of all the patient who died suddenly and could not be survived were analysed retrospectively for baseline ECG abnormality particularly Q-T-c and serum electrolyte concentration specially serum potassium concentration.

 

 

 

Observation

Total number of 234 documented sudden cardiac death (138 cases), survivor of cardiac arrest (30 cases) and ventricular tachycardia (66 cases) was observed during the study period which covered period when quinine was frequently used as drug of choice in severe malaria in 90s and 1st decade of 2000 and subsequently replaced by artemisinin derivative (artesunate IV or IM, artemether IM) group of drugs in the late half of first and second decade of 2000. All the cases were observed during the period from 1995 to 2009 with rapid decline after 2009 coinciding with period when artemisinin derivative replaced quinine as drug of choice.