Management of respiratory failure in severe neuroparalytic snake envenomation.

PN Agrawal, AN Aggarwal, D Gupta, D Behera, S Prabhakar, SK Jindal 
 Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh - 160012, India., India

Correspondence Address:
P N Agrawal
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh - 160012, India.
India

Full Text

::   Introduction

In India, approximately 15,000 persons die of bites by

poisonous snakes every year.1 The systemic effects of

venom of elapid snakes (cobra and krait) are

predominantly neurotoxic, causing a selective neuromuscular

block, affecting mainly the muscles of eyes,

tongue, throat and chest leading to respiratory

failure.[2] These patients require ventilatory assistance

in addition to administration of anti-snake venom

(ASV) and other supportive measures. We present our

experience with management of patients with severe

neuroparalytic manifestations and acute ventilatory

failure.

::   Material and methods

The study was conducted at the respiratory intensive

care unit (RICU) of Postgraduate Institute of Medical

Education and Research, Chandigarh. All consecutive

patients seen during one year period, who required

mechanical ventilation for respiratory muscle

paralysis, secondary to snake envenomation, were

included. Snake bite victims with mild neuromuscular

weakness not requiring ventilatory assistance, as also

patients with systemic manifestations other than

neuroparalysis, were excluded from the study.

Detailed history and physical examination, including

the onset and nature of symptoms, site of bite, local

reaction at the bite site and general and systemic

manifestations, were recorded for each patient.

Laboratory investigations performed at admission

included arterial blood gas (ABG) analysis,

electrocardiogram (ECG), chest radiograph, serum

biochemistry, haemogram and coagulogram.

All patients were transferred to RICU from the

emergency service and ventilated using Puritan

Bennett 7200ae ventilators. Initially, control mode

ventilation (CMV) was used; patients were gradually

switched to synchronized intermittent mandatory

ventilation (SIMV) with pressure support as

neuroparalysis recovered. Meticulous attention was

paid to asepsis, nutrition, humidification of inspired

air, regular endotracheal toiletting and continuous

monitoring of haemodynamic and respiratory

(including ABG and respiratory mechanics) variables.

An effort was made to maintain oxygen fraction in

inspired air (FiO2) at <0.5, while maintaining

adequate oxygenation (pO2 >60 mm Hg). Weaning

was accomplished by gradual reduction in the SIMV

rate and the level of pressure support, once adequate

respiratory effort had reappeared. A short T-piece trial

was given and patients were extubated if they had

normal bulbar reflexes and did not show any

worsening during the period of T-piece trial.

Polyvalent ASV (Haffkine Institute, Bombay) was

administered in a loading dose of 100 ml over 2 hours,

followed by a continuous infusion at a rate of 100 ml

ASV every 6 hours, until recovery of neurological

manifestations. Ultimate outcome measure studied

was hospital survival. Duration of ventilation, period

of neuromuscular recovery and ventilator associated

complications (if any) were also recorded.

::   Results

Twenty three victims, bitten by various snakes were

admitted to this Institute during the study period, of

whom 14 patients (13 males and one female) with

ventilatory failure were managed at RICU. Their age

ranged between 12 to 60 years. All the 14 cases had

severe neuroparalytic manifestations [Table I]. Bite

marks were seen in 10 (71.4%) and local swelling

around the site of bite was present in 3 (21.4%)

patients. On admission, all patients had evidence of

type II respiratory failure as evidenced by hypercapnia

(pCO2 > 45 mm Hg) with or without severe

hypoxaemia (pO2 < 60 mm Hg) [Table I].

ASV was administered in a median dose of 900 ml

(range 400 to 1400 ml) for a median duration of 36

hours (range 8 to 60 hours). Four of the 14 patients

(28.6%) developed urticaria during ASV infusion

which was easily controlled after slowing the infusion

rate and administration of epinephrine. Neostigmine

or other cholinesterase inhibitors were not

administered to any victim.

The median duration of mechanical ventilation was 17

hours [Table II]. 60% of the patients required assisted

ventilation for less than 24 hours. One patient, who

had sustained irreversible neurological damage before

reaching the hospital, was ventilated for 20 days.

However, he succumbed to complications related to

aspiration pneumonia and septicaemia. All other

patients improved and were discharged. None of the

other patients had any ventilator associated

complications like pneumonia or barotrauma.

The median duration of neurological recovery was 76

hours (range 10 to 120 hours) in 13 patients who

survived. None of these patients had any residual

neurological deficit at the time of discharge from

hospital. Serum sickness was notably absent in all the

9 patients, who reported for follow up 4 weeks after

discharge.

::   Discussion

Neuroparalysis leading to type II respiratory failure is

the most important cause of morbidity and mortality

in victims bitten by venomous snakes of elapidae

family.[3],[4],[5] Indian cobra (Naja naja) and common

Indian krait (Bungarus ceruleus) are two important

species of elapid snakes responsible for neurotoxic

symptoms in the victims in India.1 Post-synaptic

neurotoxins in snake venom (such as -bungarotoxin

and cobrotoxin) bind to acetylcholine receptors at

motor end plate, while pre-synaptic neurotoxins (such

as -bungarotoxin, crotoxin and taipoxin) prevent

release of acetylcholine at the neuromuscular

junction. Cobra and krait venom affect mainly the

muscles of eyes, tongue, throat and chest, leading to

respiratory failure.[2] Severity of envenomation and

progression to respiratory failure is related to several

factors such as dose of venom injected (which

depends on the mechanical efficiency of bite species

and size of snake, condition of fangs, and whether the

snake has recently fed or is injured), potency of

venom (which depends on species, age and health of

snake), anatomic location of bite (whether proximal or

distal), age, health, size and possibly immune status of

victim, and the nature and timing of first-aid and

medical treatment.[4],[5] In all such patients, timely

administration of ASV and institution of cardiorespiratory

support is associated with an excellent

outcome.[6],[7],[8],[9],[10]

All except one patient, in this study, had completely

recovered. The only patient who died, had sustained

irreversible hypoxic-ischaemic cerebral injury

because of delay in reaching the hospital. Delayed

arrival in hospital is an important factor contributing

to a fatal outcome in such victims.[5] Immediate

endotracheal intubation is necessary for airway

protection and prevention of aspiration in patients

with bulbar involvement.[11] Mechanical ventilation,

generally is easy and without complications in such

patients, as the lungs are not diseased and have normal

mechanics. In this study, the median duration of

ventilation was 17 hours. The duration of mechanical

ventilation in snake bite victims is usually short since

neuroparalysis reverses quickly with prompt

administration of ASV.[11] Infact, our aim was to wean

patients as quickly as possible because the fear of

increased risk of ventilator associated pneumonia with

prolonged ventilation. One of our patients had

developed this complication, as he was ventilated for

a very long period.

The use of ASV is mandatory, as it is the only

effective treatment for neutralisation of venom that

has entered the circulation. It is most effective when

administered within 1-4 hours after envenomation.[6]

Patients with severe poisoning require higher doses of

ASV.[4] Recently, Tariang and coworkers have also

observed that patients with neuroparalysis require

higher doses of ASV as compared to patients with

haematological complications only.[12] In the present

study, we used a median of 900 ml ASV, and could

salvage all except one patient. This dose is higher than

the one recommended in literature.[4] However, in the

absence of any clear guidelines, and in view of severe

neuroparalytic envenomation, higher doses were used

in the hope of early recovery.

Few investigators have also advocated the use of

neostigmine and related anticholinesterase drugs as a

supportive measure in the management of these

victims.13 However, there is no consensus over the

routine of such drugs.[13],[14] Anticholinesterases will act

only against the post-synaptic toxins that induce a

myasthenia-like block. They are not active against

toxins acting presynaptically. They are also not useful

if administered late, as binding of toxin to

acetylcholine receptors becomes relatively

irreversible with time. None of the patients studied in

this report received such drugs.

From these observations, we conclude that

mechanical ventilatory support, along with ASV

therapy, forms the backbone of management in

patients with respiratory failure due to severe

neuroparalytic snake envenomation. The ultimate

outcome is excellent if therapy is administered

adequately and in time.

References