Number 44, April  2007

The Professional Bulletin of  The National Poison Centre, USM

ISSN 1394-5246 


prn lat. pro-re-nata, which translates as ocassionally when required or as needed is a universal abbreviation used in the practice of medicine and pharmacy. It is the official abbreviation for The National Poison Centre of Malaysia, which stands for Pusat Racun Negara (PRN) in the Malay Language.


prn-8099 the professional bulletin of the National Poison Centre aims at providing the link between PRN and professionals as well as scientific communities as home and abroad, 1-800-88-8099 being the toll-free number to call as needed.


A periodical bulletin publised by Pusat Racun Negara, Universiti Sains Malaysia.



Dzulkifli Abdul Razak



Rahmat Awang



Razak Haji Lajis

Syed Azhar Syed Sulaiman

Haslina Hashim

Halilol Rahman Mohamed Khan

Adilah Mohamed Ariff

Sulastri Samsudin

Azaharudin Awang Ahmad

Asdariah Misnan

Nur Afni Amir



Adilah Mohamed Ariff


DTP Editor

Rosman Ahmad


www Editor

Natrah Mustapha





Doses of Animal Toxins


They may be small but scary and some are deadly. Rarely, do we hear of a death from jellyfish sting, but last year, a tourist was fatally stung by a box-jellyfish in the Malaysian water. Relatively unheard, too, are local centipede’s bite that could cause death but a case of a pregnant woman who was suspected of been bitten by this small creature has become an issue people talk about.  Even the so-called “Malaysian King of Snakes” or Raja Ular, the famous snake charmer was not spared and died after he was bitten by his own King Cobra (Ophiophagus Hannah).  Some may wonder, how dangerous are these creatures? How would we address this issue to the public? Cases like those mentioned above may invariably create fear as most people do not know the degree of toxicity from these animals’ toxins and how medical treatment can help.

Poisoning data compiled from the Information and Documentation System of the Ministry of Health reported that from the year 1999 to 2001, there are a total of 19355 admissions to government health facilities due to venomous animal bites or stings. This figure outnumbered the poisoning admissions due to two commonest substances which are the analgesics and pesticides. Poisoning involving venomous animals are quite common and healthcare providers should be prepared to treat the victim appropriately.

Generally, these venomous creatures can be found on land or in the sea or fresh water. Commonly, many people fear land creatures like snakes, scorpions and centipede, but in reality some of these species are not deadly and their bites will not cause further complications if treated properly. On the other hand, small creatures like spiders, bees, wasps, and even ants possess their own so-called ‘toxins’ that can cause reaction to hypersensitive individuals. Even if such reaction does occur, individual bitten by these creatures may need to be treated, at least on the affected part, to prevent complication like infection which sometimes may lead to death. This was suspected to happen to the pregnant woman mentioned above since Malaysian centipedes are usually not deadly. To date, Malaysia is not a home to deadly scorpions, centipedes or spiders unless brought in from elsewhere.

Some marine creatures are on their own not poisonous but their body have the ability to accumulate toxins derived from their diet. Toxins like tetrodotoxin, saxitoxin and brevetoxin are some examples of toxins that were originally found in certain marine dinoflagellates (most are the marine plankton), but later consumed by pufferfish and shell fishes, and ending up in human consumption. For instance, tetrodotoxin in pufferfish is an exceptionally lethal poison with the LD50 in rat of 8µg/kg, extrapolated as 0.08 to 0.8µg/kg to human. On the other hand, others like jellyfish, lionfish, stingray and catfish have stings that may pose hazards. In Malaysian water, two species of box jellyfish were found, namely the Chiropsalmus buitendijki and Chiropsalmus quadrigatus. Their tentacles are armed with thousands of nematocysts, the stinging cells which produce striation shape of laceration that could be fatal.  Unfortunately, antidotes for these marine toxins are not available. Although deaths have been reported due to marine venomous animals, it is still relatively low, compared to deaths from venomous snake bites.

Venomous snakes of Malaysia can be classified into three families: Viperidae, Elapidae and Hydrophiidae. They are front-fanged snakes and these fangs have grove like hypodemic needle to inject venom. Viperidae are mainly vipers such as the Malayan pit viper while the Elapidae are mainly cobras, kraits, coral snakes and the Hydrophiidae are the sea snakes. Some may classify sea snakes under Elapidae family too. While snakebites pose serious threat to the victim, complications could be overcome with the use of antivenin.

Currently, there are three types of snake antivenin available in the Malaysian hospitals.  These are the polyvalent antivenin, mainly intended for cobra bite; the Malayan pit viper antivenin and the sea snake antivenin. When used appropriately, these antivenins are effective, comparatively safe, cost-effective and life-saving. Some snake bites do not involve injection of the venom and the use of antivenin may not be required.

Anybody can be at risk just by being at the wrong place at a wrong time. In treating hypersensitive individuals, extra precaution and attention may need to be taken. Appropriate use of antivenin plus effective supportive therapy may help save life. In this issue, we want to address some of the important measures in managing snakebite cases particularly in Malaysian hospital setting where antivenin is available to be used.N


Review on Management of Snakebite in Malaysia (part 1)

By Adilah M.A, Sulastri S, Asdariah M, Azaharudin A, Haslina H, Nur Afni A





Snakebite is a common problem in Malaysia. According to a study conducted by the National Poison Centre based on the data from the Ministry of Health, Malaysia there were 7881 cases of venomous snake bites admitted to government hospitals from year 1999 to 2001. This constitutes about 40.7 percent of the total cases of venomous animals bites admitted to these hospitals. Thus, it is clear that snakebite is an important medical emergency and cause of hospital admission. The purpose of this article is to create awareness among health professionals on the nature of snakebites in Malaysia, its consequences and proper approach to managing victims of snakebite.


What are the snakes of Malaysia that are of medical importance?


Snakes can be categorized as non-venomous, mildly venomous and very venomous but the majority of them are harmless and only a small percentage is poisonous. Worldwide, only about 15% of more than 3000 species of snakes are considered hazardous to humans. In Malaysia there are at least 40 species of venomous snakes, 18 of which are front-fanged land snake while the other 22 are the sea snakes. This constitutes about 20 percent of all types of snakes (venomous and non-venomous) found in the country. For the purpose of identification and understanding the clinical manifestation and management of snakebite envenomation, these venomous snakes can be classified into 3 major families. These are the Elapidae, Viperidae and Hydrophiidae. Common examples of snakes under Elapidae family include cobras, kraits and coral snakes, while pit vipers are under the Viperidae family and sea snakes belong to the Hydrophiidae.


Based on epidemiological studies in Malaysia, the Malayan pit viper, Asian common cobra (Naja naja), Shore pit viper and Wagler's pit viper were the four commonest species of snakes associated with snake bite envenomation.


How do we identify these venomous snakes and how can we differentiate between them?


There is no simple rule to identify venomous snakes since some non-venomous one may look almost identical. However, some of the most notorious venomous snakes can be recognised by their size, shape, colour, pattern of markings, their behaviour and the sound they make. A poster attached in this issue describes physical features of each common venomous snake of Malaysia.


Snakes from Viperidae family, mainly pit vipers that can be found in Malaysia, are easily differentiated because they have triangular head that is sharply distinct from the neck. There is a heat-sensitive pit between the eyes and the nostril. Some vipers also show defensive action of tail vibration, which create audible rustling sound when they are disturbed. In term of size pit vipers are usually short and fat.


Generally, family of the Elapidae possess enlarge poison fangs at the front end of the upper jaw. It is quite difficult to recognise this family by any common external feature.

Cobra (genus Naja and Ophiophagus) can rear up and spread out hood, the hood is folded during rest. Some species of cobras have hissing sounds and can spit venom.


The kraits (genus Bungarus) and coral snakes (genus Maticora and Callophis) from the Elapidae family too are almost the same, they are generally small and slender, brightly coloured and some are banded and having small head. The kraits have almost triangular shape body (cross-sectional view).


Most sea snakes have special features like flat or oar-shaped tails for swimming. They are not so important to identify because whenever victim has been bitten with two punctures in the sea, the most possible guest is due to sea snake bite.


Another alternative to identify the type of snake is based on their fang mark on the bite site. Figure 1 indicates roughly some of the patterns of the fang marks.


Figure: 1: Pattern of snakes’ fang marks



Snake identification is highly desirable, because snake-specific antivenins are less hazardous to the patient than polyvalent antivenin. Identifying them can be very difficult if they are seen fleetingly or in poor light. Scale patterns and colours can be quite unreliable, especially for brown-coloured snakes.


What is the toxic dose of snake venom?


There is no specific toxic dose of snake venom. The quantity of venom injected varies depending on the species, size of the snake and the mechanical efficiency of the bite. Venom dosage per bite also depends on the elapsed time since the last bite, the degree of threat the snake feels, and the size of the prey. The efficiency of the bite depends on whether one or two fangs penetrated the skin or there were repeated strikes.

The snake itself can control whether to inject or not to inject the venom. However snakes do not exhaust their store of venom even after several strikes. The venom of smaller, younger vipers may be richer in some dangerous components such as those affecting haemostasis.


What are the content of snake venom and how these substances react?


Snake venom is a combination of many different proteins and enzymes. Some of the proteins are very toxic while the enzymes help to increase the prey’s uptake of toxins. Enzyme concentrations vary among species, thereby causing dissimilar envenoming. To understand the mechanism of action of the different proteins and enzymes involved, venoms may be divided into three distinct types based on their clinical effects:


1. Neurological effect (Elapidae)


Neurotoxic venom mainly act on the nervous system and respiratory paralysis may be produced once the venom interacts with the central nervous system mechanism which controls respiration ; the pain and local swelling are usually not severe. There are two groups of neurotoxins, namely the pre-synaptic and the post-synaptic neurotoxins. The pre-synaptic toxin affects the release of the acetylcholine neurotransmitters while the post-synaptic toxin competes with the acetylcholine for the receptors at the neuromuscular junction.


2. Haemorrhagic effect (Viperidae and Elapidae)


Haemostatic abnormalities are distinct features of the envenoming by many vipers and several specific factors are responsible for producing incoagulable blood.

In the vioeridae, haemorrhagic effect occurs due to the activation of the proagulants at different steps of the clotting cascade resulting in the formation of fibrin in the blood. Break down of the fibrin can result in a depletion of clotting factors causing the blood to no longer clot. Hannahtoxin in the elapidae causes hemorrhagic effect by destruction of the collagenous basement membrane and other connective tissue collagens with consequent weakening of the stability of the blood vessel wall.


3. Cytolitic effect.


Cytolytic or necrotic toxins (proteolytic enzymes and phospholipases A) and other factors may increase the permeability resulting in local swelling. They may also cause damages to cell membranes and tissues.

Other effects caused by the enzyme phospholipases A2 are hemolytic and myolitic effects due to damages of the cell membrane, endothelium, skeletal muscle, nerve and red blood cells.



What are the manifestations of envenoming?


Systemic symptoms can be detected following envenoming and must be treated as soon as possible to save the patient’s life. But, the symptoms developed are based on the type of snakes and amount of the venom that been injected into the victim. The manifestations can be divided into few categories:



Table 1: Manifestation of envenoming by type of snakes


Type of snakes

Manifestations of envenoming


(Onset varies from 30 minutes to 24 hours)


  • Visual disturbances, dizziness, faintness, collapse, shock, hypotension, cardiac arrhythmias, pulmonary edema, conjunctival edema

 Bleeding and clotting disorders

  • Bleeding from recent wounds, fang marks, venepuncture and old partly-healed wounds
  • Spontaneous systemic bleeding: from gums, epistaxis, bleeding into tears, haemoptysis, hematemesis, rectal bleeding or melena, hematuria, vaginal bleeding, bleeding into the skin and mucosa, intracranial hemorrhage and cerebral haemorrhage


(Onset varies from a few minutes to 6 hours)


  • Drowsiness, parasthesia, abnormality in smell and taste, heavy eyelid, ptosis, external opthtalmoplegia, paralysis of facial muscles and other muscles innervated by cranial nerves, aphonia, difficulty in swallowing secretions, respiratory and generalized flaccid paralysis.
  • Hematuria, acute renal failure and general paralysis may also occur after envenomation.

*Exception! King cobra envenomation may also cause bleeding and clotting disorders


(Onset varies from 5 minutes to 8 hours)


 Skeletal muscle breakdown

  • Generalized pain, stiffness and tenderness of muscles, trismus, myoglobinuria, hyperkalemia, cardiac arrest, acute renal failure


  • Loin (lower back) pain, hematuria, hemoglobinuria, myoglobinuria, oliguria/anuria,symptoms of uremia(acidotic breathing, hiccups, nausea, pleuritic chest pain)


  • may include ptosis, ophthalmoplegia, dysarthria, blurred or double vision, inability to sit unassisted, depressed muscle stretch reflexes, and flaccid paralysis. In severe cases neurotoxicity may progress to respiratory failure.


Apart from the manifestations listed above, some victims may complain of having general symptoms such as nausea, vomiting, malaise, abdominal pain, weakness, drowsiness and prostration.


Generally, the later the onset of systemic symptoms the better the prognosis (i.e., less venom absorbed). The sequence of systemic symptoms development also varies depending on the type of snakes and the extent of envenomation but usually it goes like this (Table 2).


 Table 2: Sequence of systemic symptoms development


Time lapse since bite

Systemic Signs and Symptoms

Less than 1 hour

Headache (important symptom), irritability, photophobia, nausea, vomiting, diarrhoea, confusion, coagulation abnormalities, occasionally sudden hypotension with loss of consciousness.

1 to 3 hours

Cranial nerve paralysis (ptosis, diplopia, dysphagia etc), abdominal pain, hemoglobinuria, hypertension, tachycardia, haemorrhage.

More than 3 hour

Limb and respiratory muscle paralysis leading to respiratory failure, peripheral circulatory failure with pallor and cyanosis, myoglobinuria, eventually death.


Severity of envenoming can be graded as mild, moderate and severe. Grading envenoming is a dynamic process. Over several hours, an initially mild syndrome may progress to a moderate or even severe reaction. (Table 3).


Table 3: Severity of envenoming


Grading of Envenoming

Signs and Symptoms


Local pain, edema, no signs of systemic toxicity, and normal laboratory values.


Severe local pain; edema larger than 12 inches surrounding the wound; and systemic toxicity including nausea, vomiting, and alterations in laboratory values (eg: decreased of hematocrit or platelet).


Rapid early extension of local swelling, early tender enlargement of local lymph nodes, generalised petechiae, ecchymosis, blood-tinged sputum, hypotension, hypoperfusion, renal dysfunction, changes in prothrombin time and activated partial thromboplastin time, dark brown urine and other abnormal tests defining consumptive coagulopathy.


In some cases, although the snake bites, there is no envenoming at all. This is because the snake can control the amount of venom injected. Only cause local signs and symptoms at the site of the bite are present:

  •  Fang marks at the wound ( especially 2 puncture marks )

  •  Local pain

  •  Local bleeding

  •  Bruising

  •  Inflammation ( swelling, redness, heat)

  •  Blistering

  •  Local infection, abscess formation

Venom can be considered as being injected if some of the above plus one of the signs and symptoms listed below occur:

  • Local pain (burning, bursting, throbbing)

  • Lymphangitis

  • Lymph node enlargement

  • Necrosis

Instead of biting, some cobras can spit their venom into human’s eyes. If the venom spat enters the eyes, the victim can feel an immediate and intense burning, stinging pain, followed by profuse lacrimation with production of whitish discharge, congested conjunctiva, spasm and swelling of the eyelids, photophobia and blurred vision.


On the other hand, bites by kraits and sea snakes may be painless or just causing negligible local swelling without detectable fang marks. This can be unnoticeable especially when the snake bites while the victim is sleeping or walking through long grass area and heath land.


Apart from good history taking, careful examination of the signs and symptoms is also vital in determining diagnosis and extent of envenoming.


Do we need to send urine or blood for laboratory investigations?


Yes, an early testing is indicated if signs and symptoms develop. Laboratory tests are often very helpful in determining the extent of envenoming and assessing the efficacy of antivenom. It is also vital to repeat tests even if initially normal. The test should be repeated at about 2 hours and then a further 3 hours later, to ensure late development of envenoming, particularly coagulopathy, is not missed.


The following tests should be obtained in case of snake bite:

  1.  Blood clotting test: 20 minute whole blood clotting test (20WBCT) is a bedside test to determine whole blood clotting. In the Southeast Asia region, incoagulable blood is diagnostic of a viper bite and rules out an elapid bite. Refer figure 2 for step by step instruction for this test.

  2. Urine examination: The urine should be tested to check for hematuria or myoglobinuria. Urine microscopic test will confirm whether there are erythrocytes in the urine. Red cell casts indicate glomerular bleeding. In case of sea snake envenomation, monitoring urine output and qualitative urinary myoglobin are indicated. Myoglobinuria becomes evident 3 to 6 hours following envenomation. The urine may be yellow dusky colour and test positive for protein and occult blood one hour before myoglobin is detected.

  3. Complete blood picture: Obtain complete blood count with differential.

  1. White blood cell count: An early neutrophil leucocytosis is evidence of systemic envenoming from any species.

  2. Haemoglobin concentration/haematocrit: A transient increase of haemoglobin concentration/haematocrit resulting from a generalized increase in capillary permeability.

  3.  Platelet count: Thrombocytopenia may occur in viper bites.

  1. Biochemical abnormalities:

    1. Electrolytes and renal function:

      1. Monitor serum electrolytes, blood urea nitrogen and creatinine as indicated. Creatinine, urea or blood urea nitrogen levels are raised in the case of renal failure caused by some viper and sea snake bites. Creatinine clearance may be indicated in patients with increased serum creatinine in some species of viper envenoming. Early hyperkalemia may be seen following extensive rhabdomyolysis in sea snake bites. Hence’ it is important to monitor ECG in patient with hyperkalemia or significant myotoxicity.

    2. Liver function test:

      1. Mild hepatic dysfunction is reflected in slight increases in other serum enzymes. Bilirubin is elevated following massive extravasation of blood.

      2. Obtain creatinine kinase in patient with severe swelling or evidence of compartment syndrome. Aminotransferase and muscle enzyme (creatinine kinase, aldolase etc) will be elevated and sometimes to extreme levels in the presence of myolysis (example: sea snakes bites).

  2. Extended coagulation studies: A coagulation profile which includes INR/PT and aPTT, platelet count, fibrinogen level and fibrin degradation products should be obtained after a viper envenomation. Repeat every 6 hours or as indicated to assess progression of envenoming or response to antivenom. Elapid bites are less likely to produce coagulation disturbances, but following cobra bites, especially king cobra, it may occur.

  3. Arterial blood gases and pH may show evidence of respiratory failure from neurotoxic envenoming and acidemia (respiratory or metabolic acidosis) that may occur following elapid bites. Monitor pulse oximetry and/or blood gases and pulmonary function tests (negative inspiratory force, vital capacity and FEV1) to assess respiratory function and need for intubation. Avoid the test if coagulopathy is present.


20 minute whole blood clotting test (20WBCT)

Apparatus: A new, clean, dry glass tube.

The steps are as follows and may be useful if the species is unknown or difficult to identify: 

  1. Place a few millimetres of venous blood in the vessel.

  2. Leave undisturbed for 20 minutes at room temperature.

  3. Tip the vessel once.

  4.  If blood is still liquid and runs out, it is indicative of a venom-induced coagulopathy.

  5. Inaccurate results may occur if the vessel had been cleaned previously with detergent.

  6. If there is any doubt, repeat the test and include a "control" (blood from an unexposed individual).

Figure 2: 20 minute whole blood clotting test (20WBCT)



 To be continued…(Part2) – First-aids, antivenom and supportive therapy




  1. Warrell, DA, ed. WHO/SEARO guidelines for the clinical management of snake bite in the Southeast Asian region. SE Asian J Trop Med Public Health. 1999;30(suppl 1): 1-85.

  2. Sea snakes, Asian snake – Elapidae, Asian snake – Viperidae. Poisindex ®. Micromedex® Healthcare Series Vol. 131: 2007.

  3. White, J. Overview of venomous snakes of the world. In: Dart, Richard C. ed. Medical Toxicology, 3rd ed. Philadelphia. Lippincott Williams & Wilkins; 2004:1555–1556.

  4. Thompson, C. Australian Snake Bites. Australian Anaesthesia, Nov, 2003. Available at Assessed Feb 9, 2007.

  5.  Peterson, M. Snake Bite: Pit Vipers, Clinical Techniques in Small Animal Practice [online]. 2006; 21:174-182. Available at Assessed Feb 27, 2007.

  6. National Poison Centre of Malaysia. Manual of Venomous Snakes in Malaysia, Early edition 1995.

  7. Brian, JD. & Jacob, B. Snakebite. Emedicine, July 19, 2006. Available at Accessed Feb 12, 2007.

  8. Tan, N.H. Medically Important Snakes Poisonous Snakes of Malaysia.  Prof Tan Nget Hong Home page. Available at: Assessed Feb 13, 2007.

  9. Tan N.H. Symptomatology, Treatment and Toxinology of Malayan pit viper (Calloselasma rhodostoma) venom. Prof Tan Nget Hong Home page. Available at: Assessed Feb 13, 2007.

  10. Lim, B.L. Poisonous Snakes of Peninsular Malaysia, 3rd ed. Kuala Lumpur. Malayan Nature Society and Institute for Medical Research; 1991:20-49.



 Clinical Updates


A Randomized, Double-Blind, Placebo-Controlled Trial of Antivenom for Local Effects of Green Pit Viper Bites

Author(s): Ponlapat Rojnuckarin, Walee Chanthawibun, Jureeporn Noiphrom, Narumol Pakmanee and Tanin Intragumtornchai


Source :Transactions of the Royal Society of Tropical Medicine and Hygiene, Vol 100, Iss  9, September 2006, Pages 879-884.


Abstract : The efficacy of antivenom in the treatment of severe local effects caused by viper venom remains to be determined. This study is a randomized, double-blind, placebo-controlled trial involving 28 patients bitten by green pit vipers. The patients presented with marked limb swelling, but no severe coagulopathy requiring antivenom. They were randomized into 2 groups, each to receive either equine F(ab′)2 antivenom, or placebo. Their limb circumferences were measured on days 1, 2, 4 and 6 after interventions. The percentage reduction in limb circumference was significantly better in the antivenom group compared with the placebo group, especially in the first 24 h. The reduction in pain score was similar. The plasma venom levels were not different at presentation but lower in the antivenom group 24 h after intervention. These data suggest that intravenous antivenom could accelerate local oedema resolution in humans. However, the degree is not clinically significant, and, therefore, general use is not recommended.



Neostigmine for the Treatment of Neurotoxicity Following Envenomation by the Asiatic Cobra

Author : Barry Steven Gold MD


Source : Annals of Emergency Medicine, Vol 28, Iss 1, July 1996, Pages 87-89.


Abstract : Envenomation by the monocellate cobra is usually manifested clinically as neurotoxicity and local tissue necrosis. Treatment often requires administration of large quantities of antivenin, resulting in a high incidence of serum reactions. In cases where antivenin administration may be delayed for several hours or administration is contraindicated, the use of the anticholinesterase drug neostigmine may temporarily reverse the potentially lethal neurological effects of the venom.


Penetrating Ocular Injury Caused by Venomous Snakebite
Author(s) : Chen C C, Yang C M, Hu F R, Lee Y C.


Source : Am J Opthalmol, Vol 140, Iss 3, Year 2005, Pages 544-546


Abstract : This is a case report of a 34 year old man who was bitten on his right eye by a snake identified as Deinagkistrodon acutus. Antivenom was provided but patient developed facial swelling, periorbital ecchymoses, massive subconjunctival hemorrhage, severe corneal edema, and airway edema. Emergent intubation was done; evisceration subsequently performed, and a continuously active bleeding scleral wound was found. No local infection was developed under systemic and topical antibiotics. Pathologic examination of the excised cornea showed necrosis on the endothelial side.





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Review on Management of snakebite in Malaysia