Nimal Senanayake

Publications of Nimal Senanayake

• Electrophysiological correlates of respiratory failure in acute organophosphate poisoning: Evidence for differential roles of muscarinic and nicotinic stimulation.

  Authors: Pradeepa Jayawardane, Nimal Senanayake, Nick A Buckley, Andrew H Dawson

  Clinical toxicology (Philadelphia, Pa.). 04/2012; 50(4):250-3.

  Background. Respiratory failure in acute organophosphate (OP) poisoning can occur early and also relatively late in the clinical course, and the pathophysiology of respiratory failure at theseBackground. Respiratory failure in acute organophosphate (OP) poisoning can occur early and also relatively late in the clinical course, and the pathophysiology of respiratory failure at these different phases may have important clinical implications. Objective. To compare the electrophysiological findings in patients with early and late respiratory failure following acute OP poisoning. Methods. A prospective observational case series of consenting symptomatic patients with acute OP poisoning were assessed with daily physical examinations and repetitive nerve stimulation (RNS) studies. RNS was done on right and left median and ulnar nerves at 1, 3, 10, 15, 20, and 30 Hz. Outcomes such as need for ventilation and development of intermediate syndrome (IMS) were noted. Early respiratory failure was defined as occurring within 24 hours of ingestion. Results. Seventy-eight patients were recruited for the clinical and electrophysiological study and of those 59 (75.6%) patients had ingested chlorpyrifos. Seven patients developed respiratory failure within 24 hours of ingestion with overt muscarinic signs. They had no electrophysiological abnormalities at median and ulnar nerves before intubation. Three of them later developed "forme fruste" IMS. Five other patients developed late respiratory failure after 24 hours of ingestion, and all of them showed progressive RNS changes indicating severe IMS prior to intubation. Conclusion. The normal RNS in all patients developing early respiratory failure suggests that it is due to a central nervous system (CNS) and muscarinic effect. This emphasizes the need for early rapid atropinisation as a priority, combating the nicotinic effects being less urgent. This is in contrast with the late respiratory failure, which has been shown to be associated with neuromuscular dysfunction. Further studies are needed to quantify CNS and muscarinic dysfunction to assist in the development of better treatments for the severe and early OP poisoning.

• Deep coma and hypokalaemia of unknown aetiology following Bungarus caeruleus bites: Exploration of pathophysiological mechanisms with two case studies.

  Authors: Indika Bandara Gawarammana, Senanayake Abeysinghe Mudiyanselage Kularatne, Keerthi Kularatne, Roshita Waduge, Vajira Senaka Weerasinghe, Sunil Bowatta, Nimal Senanayake

  Journal of venom research. 01/2010; 1:71-5.

  Bungarotoxin present in Bungarus caeruleus (BC) causes life threatening respiratory muscle paralysis. Deep coma and hypokalaemia have been observed in a significant proportion of patients, but theBungarotoxin present in Bungarus caeruleus (BC) causes life threatening respiratory muscle paralysis. Deep coma and hypokalaemia have been observed in a significant proportion of patients, but the cause is unknown. We postulate the likely mechanism behind these two phenomena. We studied clinical details of two patients admitted with deep coma and performed electroencephalograms (EEG) and brain stem auditory and visual evoked potentials (BAEP and VEP). Daily serum potassium was measured along with urinary potassium excretion as a marker of total extracellular body potassium. Both patients had no brain stem reflexes on admission and the EEG revealed absent alpha and delta activity and presence of dominant theta activity. Alpha rhythm returned on the 3(rd) day in one patient, while in the other it did not, and the latter patient died on the 13(th) day due to disseminated intravascular coagulation. BAEP were delayed and VEP were absent in the deceased patient. Both had low serum potassium and low urinary potassium excretion. Replacement of potassium (up to 1.5mmol/kg/day) did not improve serum potassium and urinary potassium excretion. Absent alpha and delta activity in EEG and delayed BAEP and absent VEP are suggestive of a central action of the venom on both the cortical and brain stem neurones. Persistently low serum potassium and reduced urinary potassium excretion are suggestive of intracellular shift as the causative mechanism of hypokalaemia.

• Electrophysiological correlates of intermediate syndrome following acute organophosphate poisoning.

  Authors: Pradeepa Jayawardane, Nimal Senanayake, Andrew Dawson

  Clinical toxicology (Philadelphia, Pa.). 04/2009; 47(3):193-205.

  INTRODUCTION: Organophosphate (OP) poisoning is a major global health problem. The late onset of respiratory failure associated with intermediate syndrome (IMS) is a major contributor to the highINTRODUCTION: Organophosphate (OP) poisoning is a major global health problem. The late onset of respiratory failure associated with intermediate syndrome (IMS) is a major contributor to the high morbidity, mortality, and cost of OP poisoning. This is particularly important as most poisoning occurs in the under-resourced developing world. Repetitive nerve stimulation studies. An understanding of the abnormalities observed in repetitive nerve stimulation studies during the progression and development of IMS spectrum disorder may help clinicians to utilize electrodiagnostic testing in the better management of their patients with acute OP poisoning. In addition, it will allow researchers to interpret future research that utilizes repetitive nerve stimulation as an outcome measure. A review of the clinical and experimental electrophysiological studies in the IMS shows that subclinical electrophysiological abnormalities are common, progressive, and precede the onset of the clinical IMS. Serial repetitive nerve stimulation studies have been most commonly used and are the most accessible for clinicians. Clinical and experimental studies demonstrate a progression through early initial decrement-increment patterns at high rates of stimulations, which correlate with moderate muscle weakness, to decrement-increment patterns at intermediate- and low-frequency stimulations. Progression to a combination of decrement-increment and repetitive fade patterns correlates with clinical deterioration; severe decrement pattern is usually observed immediately before the onset of respiratory failure. Although electrophysiological features closely parallel clinical severity during progression of IMS, the same is not true during recovery. Electrophysiological changes sometimes improve long before the patient recovers normal strength and respiratory function. Intermediate syndrome. Thus, IMS can be regarded as a spectrum disorder affecting the neuromuscular junction (NMJ) with two main forms: a forme fruste variety associated with mild weakness and the classical IMS with weakness of 3/5 or less than 3/5 on the Medical Research Council (MRC) grading; patients in the latter category are at risk of developing late onset respiratory failure. While IMS remains a clinically important entity, the early occurrence of abnormalities on repetitive nerve stimulation studies suggest that this is part of the continuum of nicotinic receptor stimulation. CONCLUSIONS: Reviewing the anatomical and the functional structure of the NMJ and neuromuscular transmission helps to provide an understanding of the pathophysiological nature of the neuromuscular transmission failure observed in IMS. This includes potential mechanisms of presynaptic feedback which may reduce acetylcholine release and postsynaptic receptor desensitization and provides some explanation for the time course of IMS. It also suggests other potential strategies to reduce OP-induced NMJ toxicity in which repetitive nerve stimulation is likely to be an important tool in judging efficacy.

• The spectrum of intermediate syndrome following acute organophosphate poisoning: a prospective cohort study from Sri Lanka.

  Authors: Pradeepa Jayawardane, Andrew H Dawson, Vajira Weerasinghe, Lakshman Karalliedde, Nicholas A Buckley, Nimal Senanayake

  PLoS medicine. 07/2008; 5(7):e147.

  Intermediate syndrome (IMS) is a major cause of death from respiratory failure following acute organophosphate poisoning. The objective of this study was to determine repetitive nerve stimulationIntermediate syndrome (IMS) is a major cause of death from respiratory failure following acute organophosphate poisoning. The objective of this study was to determine repetitive nerve stimulation (RNS) predictors of IMS that would assist in patient management and clinical research. Seventy-eight consenting symptomatic patients with organophosphate poisoning were assessed prospectively with daily physical examination and RNS. RNS was done on the right and left median and ulnar nerves at 1, 3, 10, 15, 20, and 30 Hz. The study was conducted as a prospective observational cohort study in the Central Province, Sri Lanka. IMS was diagnosed in ten out of 78 patients using a priori clinical diagnostic criteria, and five of them developed respiratory failure. All ten patients showed progressive RNS changes correlating with the severity of IMS. A decrement-increment was observed at intermediate and high frequencies preceding the onset of clinical signs of IMS. As the patient developed clinical signs of IMS, decrement-increment was progressively noted at low and intermediate frequencies and a combination of decrement-increment and repetitive fade or severe decrement was noted at high frequencies. Severe decrement preceded respiratory failure in four patients. Thirty patients developed forme fruste IMS with less severe weakness not progressing to respiratory failure whose RNS was characterized by decrement-increment or a combination of decrement-increment and repetitive fade but never severe decrements. Characteristic changes in RNS, preceding the development of IMS, help to identify a subgroup of patients at high risk of developing respiratory failure. The forme fruste IMS with the characteristic early changes on RNS indicates that IMS is a spectrum disorder. RNS changes are objective and precede the diagnosis and complications of IMS. Thus they may be useful in clinical management and research.

• Parallel infusion of hydrocortisone +/- chlorpheniramine bolus injection to prevent acute adverse reactions to antivenom for snakebites.

  Authors: Indika Bandara Gawarammana, S Abeysingha M Kularatne, Wasantha P Dissanayake, Ranjith P V Kumarasiri, Nimal Senanayake, H Ariyasena

  The Medical journal of Australia. 02/2004; 180(1):20-3.

  OBJECTIVE: To investigate the efficacy of continuous infusion of hydrocortisone with or without chlorpheniramine bolus against early adverse reactions to polyspecific antivenom. DESIGN AND SETTING:OBJECTIVE: To investigate the efficacy of continuous infusion of hydrocortisone with or without chlorpheniramine bolus against early adverse reactions to polyspecific antivenom. DESIGN AND SETTING: Prospective, double-blind, randomised, placebo-controlled trial at General Hospital, Anuradhapura, Sri Lanka. SUBJECTS: 52 patients with snake envenoming were randomised to receive infusion of hydrocortisone (Group A), hydrocortisone with chlorpheniramine bolus (Group B) or placebo (Group C) during the administration of antivenom. INTERVENTION: Hydrocortisone 1000 mg in 300 mL of normal saline infusion was started 5 min before and continued for 30 min after antivenom. Chlorpheniramine 10 mg intravenous bolus dose was given 5 min after commencement of antivenom. MAIN OUTCOME MEASURES: Occurrence and severity of adverse reactions to antivenom. RESULTS: Adverse reactions were observed in 80% (12/15) of Group A, 52% (11/21) of Group B, and 81% (13/16) of Group C. Reactions were mild or moderate except in two patients. A significant reduction in the number of adverse reactions was seen in Group B compared with the placebo group (difference, 29 percentage points; 95% CI, 0.2 to 58 percentage points). There was no significant difference between Group A and the placebo group. CONCLUSION: Prophylaxis with a parallel hydrocortisone infusion alone is ineffective in reducing the occurrence of acute adverse reaction to antivenom serum, but combining it with chlorpheniramine seems efficacious.

• Where is the evidence for treatments used in pesticide poisoning? Is clinical toxicology fiddling while the developing world burns?

  Authors: Nicholas A Buckley, Lakshman Karalliedde, Andrew Dawson, Nimal Senanayake, Michael Eddleston

  Journal of toxicology. Clinical toxicology. 02/2004; 42(1):113-6.

• Pesticide poisoning in the developing world--a minimum pesticides list.

  Authors: Michael Eddleston, Lakshman Karalliedde, Nick Buckley, Ravindra Fernando, Gerard Hutchinson, Geoff Isbister, Flemming Konradsen, Douglas Murray, Juan Carlos Piola, Nimal Senanayake, Rezvi Sheriff, Surjit Singh, S B Siwach, Lidwien Smit

  Lancet. 11/2002; 360(9340):1163-7.

  In parts of the developing world, pesticide poisoning causes more deaths than infectious diseases. Use of pesticides is poorly regulated and often dangerous; their easy availability also makes them aIn parts of the developing world, pesticide poisoning causes more deaths than infectious diseases. Use of pesticides is poorly regulated and often dangerous; their easy availability also makes them a popular method of self-harm. In 1985, the UN Food and Agriculture Organisation (FAO) produced a voluntary code of conduct for the pesticide industry in an attempt to limit the harmful effects of pesticides. Unfortunately, a lack of adequate government resources in the developing world makes this code ineffective, and thousands of deaths continue today. WHO has recommended that access to highly toxic pesticides be restricted--where this has been done, suicide rates have fallen. Since an Essential Drugs List was established in 1977, use of a few essential drugs has rationalised drug use in many regions. An analogous Minimum Pesticides List would identify a restricted number of less dangerous pesticides to do specific tasks within an integrated pest management system. Use of safer pesticides should result in fewer deaths, just as the change from barbiturates to benzodiazepines has reduced the number of deaths from pharmaceutical self-poisoning.

• Abnormal parameters of magnetically evoked motor-evoked potentials in patients with cervical spondylotic myelopathy.

  Authors: Nishan Sudheera Kalupahana, Vajira S Weerasinghe, Udaya Dangahadeniya, Nimal Senanayake

  The spine journal : official journal of the North American Spine Society. 8(4):645-9.

  BACKGROUND CONTEXT: Magnetic stimulation (MS), which is used to evaluate motor pathways, is helpful in evaluating cervical spinal cord compression (cervical myelopathy [CM]). Previous studies haveBACKGROUND CONTEXT: Magnetic stimulation (MS), which is used to evaluate motor pathways, is helpful in evaluating cervical spinal cord compression (cervical myelopathy [CM]). Previous studies have shown that the central motor conduction time (CMCT), which is the time taken for the nerve impulses to reach the cervical spinal roots after the stimulation of the motor cortex, is prolonged in CM. However, the duration of motor-evoked potentials (MEPs) in CM has not been studied in detail. PURPOSE: To compare the duration, CMCT and amplitude of MEPs by MS between patients with clinical and magnetic resonance imaging (MRI) features of CM and a control group. STUDY DESIGN/SETTING: A cross-sectional study done at Teaching Hospital, Peradeniya, Sri Lanka. PATIENT SAMPLE: Consecutive patients with clinical features of cervical spondylotic myelopathy, without coexisting neurological abnormality. METHODS: Transcranial and cervical spinal magnetic stimulation were performed on 21 patients with clinical and MRI features of spondylotic CM (mean age, 43.5years; range, 36-63 years; 9 men) and 17 healthy volunteers (mean age, 39.05 years; range, 23-54yrs; 6 males) using a circular coil with a Magstim 200 stimulator. MEPs were recorded over abductor digiti minimi muscle on both hands. RESULTS: Seventeen patients had upper motor neuron (UMN) features in all four limbs; in the others, both lower limbs and one upper limb were affected. The upper limbs with UMN features had shorter duration MEPs compared with the control group. The CMCT and the total motor conduction time were also delayed in the CM group. All three differences were very highly significant (t=5.75, -3.76, 5.27; p<.001). The amplitudes showed no significant difference between the two groups (t=1.27, p=.208). CONCLUSION: This study shows that in addition to the CMCT, the duration of MEPs is also useful in evaluating patients with CM using MS.