Cleistanthus Collinus Poisoning
QTc PROLONGATION AS A PROGNOSTIC MARKER IN CLEISTANTHUS COLLINUS POISONING
DISSERTATION SUBMITTED FOR
M.D GENERAL MEDICINE
BRANCH – I
APRIL 2020 REGISTRATION NUMBER - 201711119
THE TAMILNADU DR.M.G.R. MEDICAL UNIVERSITY CHENNAI, TAMILNADU, INDIA CERTIFICATE FROM THE DEAN
This is to certify that this dissertation entitled “QTc PROLONGATION
AS A PROGNOSTIC MARKER IN CLEISTANTHUS COLLINUS
POISONING” is the bonafide work of Dr.G.SHANTHOSH in partial fulfillment of the university regulations of the Tamil Nadu DR. M.G.R. Medical
University, Chennai, for M.D General Medicine Branch I examination to be held in April 2020.
Dr.K.VANITHA, MD, DCH, The Dean, Madurai Medical College, Madurai. CERTIFICATE FROM THE HOD
This is to certify that this dissertation entitled “QTc PROLONGATION
AS A PROGNOSTIC MARKER IN CLEISTANTHUS COLLINUS
POISONING” is the bonafide work of Dr.G.SHANTHOSH in partial fulfillment of the university regulations of the Tamil Nadu DR. M.G.R. Medical
University, Chennai, for M.D General Medicine Branch I examination to be held in April 2020.
Dr. M. NATARAJAN, M.D., Professor and HOD, Department Of General Medicine, Government Rajaji Hospital, Madurai Medical College, Madurai. CERTIFICATE FROM THE GUIDE
This is to certify that this dissertation entitled “QTc PROLONGATION
AS A PROGNOSTIC MARKER IN CLEISTANTHUS COLLINUS
POISONING” is the bonafide work of Dr.G.SHANTHOSH in partial fulfillment of the university regulations of the Tamil Nadu DR. M.G.R. Medical
University, Chennai, for M.D., General Medicine Branch I examination to be held in April 2020.
Dr. J. SANGUMANI, M.D, D.DIAB, Professor of Medicine, Department Of General Medicine, Government Rajaji Hospital, Madurai Medical College, Madurai. DECLARATION BY THE CANDIDATE
I declare that, I carried out this work on “QTc PROLONGATION AS A
PROGNOSTIC MARKER IN CLEISTANTHUS COLLINUS
POISONING” at the Department of Medicine, Govt. Rajaji Hospital during the period FEBRUARY 2019 TO JULY 2019 under the guidance and supervision of Prof. Dr. J.SANGUMANI.M.D, D.DIAB,. I also declare that this bonafide work or a part of this work was not submitted by me or any others for any award, degree or diploma to any other University, Board either in India or abroad.
This dissertation is submitted to The Tamil Nadu DR. M.G.R. Medical
University, Chennai in partial fulfillment of the rules and regulations for the award of M.D Degree General Medicine Branch- I; examination to be held in
April 2020.
Place : Madurai Dr. G.SHANTHOSH, Date : Post Graduate student, Department of General Medicine, Madurai Medical College
ACKNOWLEDGEMENT
I would like to thank Dr. K. VANITHA, MD, DCH., Dean, Madurai
Medical College, for permitting me to utilize the facilities of Madurai Medical
College and Government Rajaji Hospital for this dissertation.
I wish to express my respect and sincere gratitude to my head of department, Prof. Dr. M. NATARAJAN M.D., Professor of Medicine for his valuable guidance and encouragement during the study and also throughout my course period.
I would like to express my deep sense of gratitude, respect and thanks to my beloved Unit Chief and Professor of Medicine Prof. Dr. J. SANGUMANI
M.D, D.DIAB, for his valuable suggestions, guidance and support throughout the study and also throughout my course period.
I am greatly indebted to my beloved Professors
Dr. G. BAGHYALAKSHMI M.D., Dr. C. DHARMARAJ, M.D.,
Dr. DAVID PRADEEP KUMAR M.D, DGM, MRCP.,
Dr. S.C. VIVEKANANTHAN M.D, DTCD., and Dr.K. SENTHIL M.D., for their valuable suggestions throughout the course of study.
I express my special thanks to Prof. Dr. M. NATARAJAN M.D,
Professor and HOD Department of Medicine for permitting me to utilize the facilities in the Department, for the purpose of this study and guiding me with enthusiasm throughout the study period.
I am thankful to my Assistant Professors:
Dr. R. PALANI KUMAR M.D.,
Dr. P. SUDHA M.D.,
Dr. M. SURESH KUMAR M.D.,
for their valid comments and suggestions.
I sincerely thank all the staffs of Department of Medicine and
Department of biochemistry for their timely help rendered to me, whenever and wherever needed.
I extend my love and express my gratitude to my family and friends for their constant support during my study period in times of need.
Finally, I thank all the patients, who form the most vital part of my work, for their extreme patience and co-operation without whom this project would have been a distant dream and I pray God, for their speedy recovery.
CONTENTS
S.NO CONTENTS PAGE NO
1 INTRODUCTION 1
2 AIM OF STUDY 2
3 REVIEW OF LITERATURE 3
4 MATERIALS AND METHODS 60
5 RESULTS AND OBSERVATIONS 64
6 DISCUSSION 79
7 CONCLUSION 81 ANNEXURE
BIBLIOGRAPHY
PROFORMA
ABBREVATIONS
MASTER CHART
ETHICAL COMMITTEE APPROVAL LETTER
ANTI PLAGIARISM CERTIFICATE
INTRODUCTION
Cleistanthus collinus is a shrub that grows in many areas in south India.
The shrub is also grows in Malaysia and Africa. It is called as Oduvanthalai in
Tamil Nadu. Any part of the plant is toxic. It is commonly used as a homicidal agent and abortifacient. It can be ingestion by swallowing the crushed plant parts, chewing leaves or a decoction of the boiled leaves. The toxic compounds are arylnaphthalene lignan compounds like Cleistanthin A; B which are responsible for most of the clinical features. The other toxic compounds are Diphyllin and cleistanthin C and D. In the kidneys, it causes distal Renal Tubular Acidosis resulting in hypokalemia and also normal anion gap metabolic acidosis. Cardiac involvement results in arrhythmias.
Plant poisoning is a common method of self-harm in rural young women in South India. The most common plant poisons consumed in South India are
Cleistanthus collinus and Thevetia peruviana. Women consume plant poisons because of easy availability or free access. Though the plant grows in other parts of the country, poisoning is confined mainly to the southern parts of the India.
1
AIM OF THE STUDY
TO STUDY THE INCIDENCE OF QTc PROLONGATION IN
CLEISTANTHUS COLLINUS POISONING.
TO STUDY THE USEFULNESS OF QTc PROLONGATION AS A
PROGNOSTIC MARKER IN CLEISTANTHUS COLLINUS POISONING.
2
REVIEW OF LITERATURE
India is a tropical country, and so, it is host to a rich array of thousands of plants, some of them are extremely poisonous. Most people in rural areas depend for their food, on plants grown in their own farms. Cases of accidental poisoning occur frequently due to careless ingestion of toxic plant products or contamination of food items. Some cases are due to, consumption of harmful home remedies or traditional treatment. A substantial number of patients are children, for whom plants are accessible easily. In few Western population, most of the human exposures reported to poison, are involving plants. In India, if rural population is taken in isolation, the percentage of consumption of plant poisons will be very high.
3
Cleistanthus collinus poisoning
The shrub is also called, Oduvanthalai or Nillipalai in Tamilnadu and
Pondicherry, Kadishe in Andhra Pradesh, Karlajuri in West Bengal, Garari
in northern states of India
Its botanical name is Cleistanthus collinus.
Cleistanthus collinus belongs to family Phyllanthaceae and grows wild in
dry hills of India from Himachal Pradesh to Bihar and also in southern
parts, upto peninsular India.
It is a small, deciduous tree with spreading and smooth branches. Leaves
are orbicular or broadly oval or elliptical and has rounded tips.
Flowers look like borne in small axillary clusters.
The fruit capsule is large, looks trigonous, woody, dark- brown and appears
shiny and wrinkled when dried.
Seeds look globose and chestnut to brown in colour.
4
Toxic parts of the plant include all parts of the plant, which are equally
poisonous.
Extract of the various parts of the plant yield a number of compounds.
Of these, glycosides, arylnaphthalene lignan lactones are highly toxic.
The lignan lactones including cleistanthin A and B, collinusin and
diphyllin, are called collectively as “oduvin”.
Clinical features include
1. Vomiting
2. epigastric pain
3. breathlessness
5
4. visual disturbances, giddiness and drowsiness
5. fever, tachycardia, hypotension or
6. respiratory arrest
7. survivors are usually asymptomatic or transiently symptomatic with
abdominal pain, giddiness or visual symptoms.
Neuromuscular weakness may be documented.
Distal renal tubular acidosis and shock occurs due to inappropriate
vasodilatation.
Diagnosed by
1. ECG changes like QTc prolongation and non-specific ST-T changes.
2. Blood investigations may reveal hypo-kalaemia, hypo-natraemia, hyper-
bilirubinaemia, hypo-calcemia and elevated urea levels.
3. Arterial blood analysis, may show metabolic acidosis, hypoxia with a
widened alveolar- arterial O2 gradient, especially in those with respiratory
failure.
Treatment can be given by,
1. Correction of metabolic acidosis with soda bicarbonate.
2. Correction of hypokalaemia with intra-venous potassium chloride.
3. N-acetylcysteine in the form of i.v., given as 150 mg/kg i.v. over 1 hour,
followed by 50 mg/kg i.v. over 4 hours and 100mg/kg i.v. over the next 16
hours.
6
7
8
Castor poisoning
It is commonly known as, mole bean or moy bean or palma christi.
Its botanical name is Ricinus communis.
The plant belonging to family Euphorbiaceae, which is a perennial, erect,
branched plant, native to India. It is also encountered even in temperate
and tropical climates.
Dwarf forms of the plant are typically 2 metres in height, however most
plants become tree-like with stout roots and soft stems reaching a height of
7 to 8 metres.
Stems and branches are red or maroon.
Leaves have long, green or reddish stalks and are quite large, which are
generally notched into several palmate lobes with toothed margins.
Clusters of greenish-white coloured flowers form at the end of the
branches, on long upright stems. Male and female flowers are separate, but
on the same plant.
The fruit (seed pod) has a prickly capsule.
The fruit contains three shiny, mottled, hard-coated, greyish-brown seeds.
9
Seed pods are green or red, an inch long, and holds elliptical, glossy seeds,
which may be mottled with black, brown, white colours, and are 1.5cm in
length.
Used as an ornamental plant.
Oil extracted from the seeds is used medicinally as a purgative and as a
lubricant oil for engines.
Castor beans have found use, both systemically and topically.
Used in stimulating breast milk production in many countries.
10
Ricin is being used as a chemical warfare agent and also as a reagent for
pepsin and trypsin
Toxic parts of the plant are seeds
The toxic principle is the phytotoxin ricin which is a toxalbumen.
Toxalbumen is not present in castor oil, contains a milder irritant, ricinoleic
acid. Ricin is a supertoxic poison of plant origin.
Toxalbumens cause severe gastrointestinal irritation, especially of the
oropharynx, oesophagus, or stomach when exposed.
Although clinically similar to alkaline caustic burns, they are usually
delayed for few hours after exposure.
11
Delayed complications occur from the cytotoxic effects on the liver, central
nervous sytem, kidney, and adrenal glands, typically 2 to 4 days after
exposure.
The patient may be asymptomatic initially.
The seeds are harmless when ingested whole, since the outer coating resists
digestion.
But, if the seeds are crushed or chewed before swallowing, toxicity results
due to the release of ricin.
Poisoning is severe, when ricin is injected parenterally.
Ricin has two polypeptide chains held together by a single disulphide bond
with a molecular weight of 66,000.
Chain B is a lectin that binds to the surface of the cell, facilitating toxin
entry into the cell.
Chain A disrupts protein synthesis by activating the 60S ribosome.
Sensitisation to castor bean may occur, with the main allergen being a
storage albumin. Both Type 1 (immediate) and Type IV (delayed) reactions
have been reported.
Haemagglutination is almost never seen in actual poisonings.
12
It is now believed that the haemagglutinating agent is not ricin, but another
lectin, ricine.
The pulp of the seed contains allergic glycoproteins which cause allergic
dermatitis, rhinitis and asthma in some individuals.
Clinical features
1. There is a delay of several hours before manifestations begin.
2. There is a burning sensation in the GI tract which is followed by colicky
abdominal pain, vomiting and diarrhoea.
3. Frequent stools, including bloody diarrhoea and tenesmus, can occur.
4. There is haemorrhagic gastritis and dehydration.
5. Blood Urea Nitrogen, amino acid hydrogen, and inorganic phosphate
levels are elevated.
6. CNS toxicity can occur, involving the cranial nerves. Optic nerve damage
is been reported with ricin.
7. Renal manifestations include acute renal failure and haematuria . Serum
creatinine is usually elevated.
8. Liver damage may occur in higher doses.
9. Alterations in glucose metabolism has to occured in experimental ricin
intoxication. GI absorption of glucose decreases and glucose
concentrations fall.
13
Fatal dose is believed to be the ingestion of a single castor seed, whereas
actually 8 to 10 seeds are required to result in death.
However, even a single seed can occasionally cause death resulting from
anaphylaxis.
Parenteral injection of ricin is fatal with a dose as low as 1 mg/kg predicted
body weight.
However, ricin is a poorly absorbed substance, and it may take up to 5 days
for toxic effects to manifest completely.
Treatment in the latent period between exposure and systemic symptoms
requires observation for 8 hours following exposure to ricin.
Decontamination procedures include stomach wash, activated charcoal
and catharsis.
Supportive measures consist of i.v. fluids, monitoring for hypoglycaemia,
haemolysis and complications of hypovolaemia.
Alkalinisation of urine prevents crystallisation of haemoglobin and it
should be considered in severe poisonings.
Many antidotes have been suggested, but no specific treatments are
available for toxalbumen exposures.
14
Croton poisoning
The botanical name is, Croton tiglium.
The plant belonging to family Euphorbiaceae, found in, Assam, Bengal,
and the Western Ghats.
It’s a small tree with ovate or elliptic leaves which are narrow-pointed,
toothed, and 2 to 3 inches long, varying from metallic green to bronze,
orange or yellow.
Seeds are oval, smooth, 2 cm long, and brownish in colour.
The seed, oil, and root extract are used as a laxative.
Toxic parts of the plant include,
1. Stem,
2. leaves,
3. seeds.
Toxic principle is Crotin or toxalbumen and Crotonoside which is a
glycoside.
Clinical features include,
Plants in this family contain irritant contains diterpene esters that are
strongly irritative.
Rubbing the latex of these plants on face or chewing on the stem results
in erythema, swelling, and blistering.
15
Initial symptoms of reddening and swelling occur in 8 hours, with vesicle
and blister formation peaking in 4 to 12 hours.
Severity depends on the amount of latex and the duration of contact.
Ingestion results in burning pain in the upper GI tract, vomiting,
tenesmus, watery or blood-stained diarrhoea.
Severe diarrhoea results in hypotension, collapse, coma, and death.
Treatment includes,
1. Decontamination with gastric lavage.
2. Treatment of shock with i.v. fluids and vasopressors.
3. Administration of cold milk may alleviate the GI irritation.
16
Glory Lily Poisoning
Botanical name of the plant is Gloriosa superba
Other common names include,
1. Climbing lily
2. Superb lily.
The plant belongs to family Liliaceae, which is a large, herbaceous,
climbing annual.
It has a slender vine with a thick tuberous root, resembling that of a sweet
potato.
The leaves terminate in tendril-like, long, curling tips.
It’s flowers are large, solitary, yellow or red, crinkled, and long-stalked.
They appear to be “upside-down”, with the stamens and pistils pointing
downwards.
It’s uses are,
1. The juice from the leaves is used as a pediculoside.
2. The root is used to treat various ailments in traditional medicine.
Toxic parts of the plant are leaves and root.
17
Toxic principles are,
The roots containing colchicine and gloriosine.
The tubers contain an estimated 6 mg/10 gm of tuber of colchicine, along
with gloriosine, which is a related alkaloid.
Clinical features include,
1. Acute poisoning with the root results in severe vomiting, diarrhoea,
tachycardia, chest and abdominal pain.
2. Hypotension, bradycardia.
3. Seizures.
4. Bone marrow suppression.
5. Coagulopathy.
6. ECG changes, respiratory failure and death have been reported.
Acute colchicine overdose results in severe toxicity which may be delayed
for 12 hours post ingestion.
Toxic effects occur in three phases.
Early Phase upto 24 hours,
1. Severe GI symptoms like nausea, vomiting, abdominal pain, haemorrhagic
gastroenteritis along with electrolyte abnormalities, volume depletion, and
hypotension.
2. Ingestion causes numbness of the lips, tongue and throat.
18
Second phase extends up to 72hours.
1. Multisystem organ failure, with fever and neurological features like,
confusion, coma and ascending peripheral neuropathy.
2. Pulmonary, renal, hepatic, haematological and cardiovascular toxicity.
3. Seizures have been reported in children.
4. Death may occur from respiratory failure, cardiovascular collapse, or
sudden cardiac death.
5. Sepsis is the most common cause of death between 3 to 7 days.
Third phase extends up to 7 to 10 days.
Phase of recovery is characterised by a rebound leukocytosis and reversible
alopecia.
The fatal dose used is, estimated fatal dose of pure colchicine being 7 to 60
mg.
The colchicine content of tubers of Gloriosa superba is approximately
0.4%.
A potentially lethal amount would therefore be contained in about 5 grams
of tuber.
Radioimmunoassay and enzyme linked immune-sorbent assays have also
been developed for detecting colchicine.
19
Treatment includes,
1. Following an ingestion, the patient should be observed for at least 12 hours
due to an asymptomatic period, which can last up to 12 hours.
2. Decontamination involes activated charcoal therapy.
3. Colchicine is believed to undergo enterohepatic circulation.
4. Activated charcoal may interrupt enterohepatic recirculation, though there
is no clinical evidence that this decreases toxicity.
5. Symptomatic and supportive measures like fluid and electrolyte
management
6. Potassium levels, should be followed closely, while administration of
appropriate IV fluids.
7. A complete blood count should be done daily, monitoring for bone marrow
depression.
8. Patients suffering from bone marrow depression should be isolated to
prevent the patient developing infection.
9. Analgesics or opiates with an anticholinergic drug, if necessary may be
used to control abdominal pain.
10. Ascending paralysis with respiratory involvement requires mechanical
ventilation.
20
Figure - The Gloriosa superba plant with presence of flowers.
21
Marking Nut poisoning
The botanical name is Semecarpus anacardium.
This tree belongs to the family of Anacardiaceae.
It grows well in many parts of the country, and bears oblong leaves
rounded at the tip, ash grey in colour, with cartilaginous margins.
The fruit is also called “marking nut”.
It is blackish in colour and is vaguely heart-shaped. The juice of the nut
being oily and black.
The juice of the nut is used to mark washed laundry and hence the name
marking nut.
The nut is used to treat various ailments in folk medicine.
The bruised nut is sometimes used as an abortifacient, by inserting it
into the vagina.
Toxic principles include
1. Semecarpol
2. Bhilawanol.
22
Clinical features include,
1. Skin contact with the acrid juice results in irritation, vesication and
ulceration.
2. Ingestion produces GI distress with blister formation in and around the
mouth.
3. Severe poisoning results in vomiting, abdominal pain, diarrhoea,
hypotension, tachycardia, delirium, and coma.
4. Pupils may be dilated.
Fatal dose is 5 to 8 seeds, or 10 grams.
Treatment comprises of,
1. Wash contaminated skin with soap and water, and treat lesions with help
of a dermatologist.
2. Decontamination, if taken orally, with activated charcoal and laxative.
3. Milk may be useful in ameliorating the GI distress.
4. Supportive and symptomatic measures.
23
Mayapple (May Apple) Poisoning
Common name of the plant is American Mandrake.
Botanical plants include,
1. Podophyllum peltatum,
2. Podophyllum hexandrum.
This plant belonging to family Podophylaceae grows well in the hilly
regions of Sikkim, Uttar Pradesh, Punjab, Himachal Pradesh, and Kashmir.
It is a towering herb with a root stock with deeply lobed leaves having
toothed margins.
Flowers are usually single, cup-shaped and white or pink in colour.
Fruits are generally ovoid and bright scarlet.
Toxic Part include leaves and rhizomes.
Toxic Principle is podophyllin
Podophyllin or the purified form, podophyllotoxin is an amorphous caustic
powder which is light brown to greenish- yellow or brownish-grey in
colour having a characteristic odour and is a mixture of compounds divided
into two groups: lignans (wood extracts) and avonols.
It is present in the rhizomes and roots of the plant, and contains
podophyllotoxin.
24
Commercial preparations usually contain 25% podophyllum resin as
tincture of benzoi or 10% benzoin and isopropanol.
Both podophyllum and podophyllotoxin, have a colchicine-like and
vinblastine-like effect, resulting in the chemical effects of,
1. Antimitosis, which is arrest of mitosis in metaphase.
2. Negative effect on axoplasmic transport.
3. Inhibition of protein, RNA and DNA synthesis.
4. Blocking of oxidation enzymes in tricarboxylic acid cycle.
25
Uses of the plant includes,
1. Podophyllum and its resin, used as keratolytic agents whose caustic action
is thought to be caused by the arrest of mitosis in metaphase.
2. Topical treatment of venereal warts.
3. Podophyllum is also used in Homoeopathy.
Clinical features have a varied presentation,
1. Ingestion or dermal application, both result in toxicity.
2. The toxicity associated with podophyllum are colchicine-like, arresting
cellular mitosis.
3. Symptoms usually begin 30 minutes to several hours following ingestion
and 24 hours following dermal absorption.
4. Exposure of eyes to podophyllum powder causes intense irritation with
conjunctivitis, keratitis, corneal ulceration and iridocyclitis.
5. Ingestion results in nausea, abdominal pain, vomiting, and diarrhoea,
followed by fever, tachypnoea, peripheral neuropathy,
6. Severe poisoning resulting in tachycardia, hypotension, ataxia, dizziness,
lethargy, confusion, and altered sensorium.
7. Seizures may occur.
8. Polyneuropathy generally appears in a week and progresses for 2 to 3
months.
26
9. After a few days, pancytopenia and hepatic dysfunction may occur, which
generally resolves in 2 to 3 weeks.
10. Cardiotoxicity, ileus, coma and hallucinations may occur.
11. Autonomic dysfunction, including sinus tachycardia, urinary retention,
paralytic ileus, and orthostatic hypotension may persist for several months.
12. Oliguria, anuria, and renal failure are rare complications.
13. Consumption of Chinese herbal products containing extracts of
podophyllum have caused neuropathy and encephalopathy.
It has been suggested that podophyllum should not be used during
pregnancy for the treatment of genital warts due to the potential for severe
myelotoxicity and neurotoxicity in the mother.
There are indications that podophyllum may be teratogenic and
carcinogenic.
Squamous cell carcinoma- like changes have been reported following the
dermal use of podophyllum in humans.
Treatment comprises of
1. Baseline investigations including, CBC, Sr. electrolytes, Sr. calcium, renal
function test and liver function test.
2. Gastric decontamination with induced emesis is not indicated, although
activated charcoal might help.
3. Symptomatic and supportive measures.
27
4. For hypotension, Infuse 10 to 20 ml/kg of isotonic fluid.
5. If hypotension persists, administer dopamine or noradrenaline.
6. Monitor electromyography and nerve conduction studies in all patients
with symptoms of peripheral neuropathy.
7. Patients generally recover from thrombocytopenia and leukopenia within
a month.
8. Granulocyte colony-stimulating factor- filgrastim may be effective in
accelerating recovery from neutropenia following podophyllum poisoning.
9. Due to the large molecular weight of the compound it is unlikely that
haemodialysis would be effective, for the removal of podophyllum.
10. Early haemoperfusion has been suggested by some, to be useful in
facilitating neurological recovery in some patients. But there is no
conclusive data regarding its usefulness.
28
Rosary pea poisoning
Common names of the plant include, Jequirity bean, Indian bead,
Buddhist rosary bead, Rosary pea, Seminole bead, Prayer bead, Jungle
bead, Crab’s eye, Weather plant, Love bean, Lucky bean, Ojo de pajaro
and Indian liquorice.
The botanical name is Abrus precatorius.
Physical appearance shows,
The green vine belongs to family Leguminosae and is a tropical,
ornamental, twining, woody vine which grows to a height of 20 feet when
supported by other plants.
It has slender, tough branches with 10 cm long compound leaves bearing
10–20 pairs of leaflets.
Leaves are alternate, opposite, pinnately divided with small oblong
leaflets. Leaflets appear in 8 to 15 pairs and are about half inch long.
Stems are green but later develops grey bark as the plant matures.
Flowers are pink, purple or white and borne in clusters. They appear in the
leaf axils along the stems.
The distinctive part of the plant is the seed which is oval and has an
attractive hard glossy outer shell that is usually scarlet red with a black
centre.
29
The seeds are present inside fruit pods, each containing many seeds. The
pods split-open when ripe.
The pod is a legume (pea-shaped pod) and is about 3 cm long.
The seeds are often used in rosary beads, necklaces, and folk jewellery.
Jewellers in India, sometimes use the seeds as a measure for weighing gold
or precious stones.
30
Quacks use extracts of various parts of the plant, for the treatment of a wide
variety of ailments.
Toxic parts include, Seeds, root and leaves.
The toxic principles are,
1. Abrin, abric acid, glycyrrhizin and N-methyl tryptophan.
2. The main active principle is abrin, which is a toxalbumen very similar to
ricin.
3. It is a lectin composed of two polypeptide chains, A and B that are
connected by a disulphide bridge.
4. The basic structure of two peptide chains linked by a single disulphide
chain is similar to that of botulinum toxin, tetanus toxin, cholera toxin,
diphtheria toxin and insulin.
5. Like castor, the seeds of abrus are harmless when ingested whole, since the
hard outer shell resists digestion.
6. However, crushing of the seed before swallowing will enable the toxins to
be released.
7. Abrin is a powerful gastrointestinal toxin and one of its polypeptide chains
(B) binds to the intestinal cell membrane, while the other chain, (A) enters
the cytoplasm.
8. Once inside the cell, the A chain acts on the 60S ribosomal sub-unit,
prevents binding of elongation factor 2, thus inhibiting protein synthesis
and leading to cell death.
31
Clinical features include,
1. Dermal contact causes redness and rash.
2. Ocular exposure causes redness, swelling and blindness.
3. Ingestion causes, burning pain in the mouth and throat; severe vomiting;
abdominal pain and bloody diarrhoea.
4. Cardiac arrhythmias
5. CNS manifestations like headache, convulsion and CNS depression.
6. Elevations of liver enzymes.
Usual fatal dose is about 1 to 2 seeds.
There have been cases of ingestion of large amounts of seeds, which have
resulted in minimal clinical effects. This may represent variations in
toxicity, and GI absorption.
If the seeds of these plants are swallowed as a whole, symptoms are less
likely to occur.
Treatment includes,
1. Gastric decontamination in the form of lavage or activated charcoal.
2. Whole bowel irrigation is said to be helpful, according to some
investigators.
3. Supportive measures, with special emphasis on i.v. fluids.
32
Sweet Pea Poisoning
Common names of the plant are, Chickling pea, Indian pea, Grass pea and
Guaya.
Botanical name is Lathyrus sativus.
The plant belongs to a family of Leguminosae, which grows well in
Madhya Pradesh, Bihar, Uttar Pradesh, West Bengal and Punjab.
The seeds also called kesari dal, are used as a substitute for lentils by the
rural folk in these states.
Toxic principles are,
1. Beta-N-oxalyl-amino-L-alanine (BOAA).
2. Beta- N-oxalyl-alpha-beta-diaminopropionic-acid.
Clinical features are,
Chronic intake of kesari dal leads to the development of lathyrism,
characterised by progressive bilateral spastic paraparesis.
There may be prodromal manifestations such as cramps, prickling
sensation, and nocturnal calf pain.
Tendon reflexes are usually exaggerated and plantar response is extensor.
Treatment -Exclusion of kesari dal from diet and symptomatic measures.
33
Figure - Lathyrus sativus
34
QT interval
35
The QT interval is measured, from the beginning of the QRS complex to
the end of the T wave.
The ACC / AHA/ Heart Rhythm Society recommend that the QT interval
should be measured using at least three different leads and should be the
longest QT interval that can be measured in the 12-lead ECG.
The duration of the QT interval is affected by heart rate (HR).
Thus, the QT interval corrected for heart rate known as the QTc.
The QTc is calculated using the Bazett formula.
The normal QTc is longer in women than in men.
The QTc interval, should not exceed 0.44 seconds (440 milliseconds) in
women and 0.42 seconds (420 milliseconds) in men.
A prolonged QT interval is defined as a QTc >0.44 seconds (440
milliseconds) in men and >0.46 seconds (460 milliseconds) in women and
children.
If bundle branch block or intraventricular conduction defect of >0.12
seconds is present, the QTc is prolonged if it measures >0.50 seconds (500
milliseconds).
36
A prolonged QTc interval can be either, acquired or inherited.
It predisposes to the occurrence of, a ventricular arrhythmia called torsades
de pointes which is a Polymorphic VT.
A prolonged QTc, either acquired or inherited, should always be identified
because it can be lethal.
The difference between the longest and shortest QT interval, when the QT
intervals are measured in all leads in a 12- lead ECG, is called QT
dispersion.
Wide QT dispersion of >100 milliseconds predicts a patient who is prone
to ventricular arrhythmias.
37
Bazett's formula
The most commonly used QT correction formula is the Bazett's
formula, named after physiologist, Henry Cuthbert Bazett, calculating the
heart rate corrected QT interval (QTc).
Bazett's formula is based on observations from his study, in 1920.
Bazett's formula is given in a form that returns QTc in dimensionally
suspect units, square root of seconds. The mathematically form of Bazett's
formula is,
Where, QTc is the QT interval corrected for heart rate, and RR is the
interval from the onset of one QRS complex to the onset of the next QRS
complex.
This mathematically correct formula returns the QTc in the same units as
QT, which is in milliseconds.
In this formula, it is assumed that QT is measured in milliseconds and that
RR is measured in seconds, often derived from the heart rate (HR) as
60/Heart Rate.
38
Therefore, the result will be given in seconds per square root of
milliseconds. However, reporting QTc using this formula creates a
requirement regarding the units in which the original QT and RR are
measured.
In either form, Bazett's non-linear QT correction formula is generally not
considered accurate, as it over-corrects at high heart rates and under-
corrects at low heart rates.
Bazett's correction formula is one of the most suitable QT correction
formulae for neonates.
Once corrected, a QTc > 440msec in males and > 460msec in females is
considered prolonged.
39
Acquired Long QT syndrome
Drugs – Ketoconazole, tetracycline, erythromycin.
Neurogenic.
Severe hypothermia.
Hypokalemia.
Hypocalcemia.
Coronary contrast injection.
Class 1A and class 3 anti-arrythmic drugs.
Severe bradycardia.
Advanced AV block.
Myocardial ischemia.
Unexplained.
40
Congenital Long QT syndrome
Familial prolongation of the QT interval associated with, congenital
deafness and sudden cardiac death due to ventricular arrhythmia was first
reported by Jervell and Lange-Nielsen.
This condition is autosomal recessive.
Romano-Ward syndrome is an autosomal-dominant congenital long QT
syndrome, associated with sudden death and normal hearing.
The disorder has incomplete penetrance, the appearance of symptoms is
sporadic, and the duration of the QT interval shows marked variations.
Syncope and sudden death are provoked by sympathetic stimulation and
emotional stress, such as fright or startling noises.
Prolongation of the QT interval is precipitated by noxious stimuli, followed
by concomitant appearance of VPC’s and ventricular tachycardia
degenerating into ventricular fibrillation.
Evidence for autonomic dysfunction in patients with long QT syndrome
include an inability to increase the heart rate appropriately with exercise
and inappropriate adjustment of the QT interval to tachycardia induced by
exercise.
Polymorphic VT (torsade de pointes) or ventricular fibrillation, occur in
the setting of large dispersion of ventricular repolarization and are
precipitated usually by a VPC interrupting the T wave.
41
Congenital long QT syndrome (LQTS) is an abnormality of ion channel,
that can be, K+ channel block or prolonged inactivation of the Na+
channel.
Mutations in two genes where common in some affected families, both
encoded cardiac channels in families linked to chromosomes 3 and 7.
Congenital LQTS is primarily a channelopathy with genetic heterogeneity.
The Jervell and Lange-Nielsen syndrome is caused by two genes that
encode the slowly activating delayed rectifier potassium channel KCNQ1
and KCNEI.
The Romano-Ward syndrome is caused by mutations in eight different
genes,
1. KCNQI (LQTI),
2. KCNH2(LQT2),
3. SCN5A (sodium channel-LQT3),
4. ANKB (protein ankyrin involved in anchoring calcium and sodium
channel to the cellular membrane (LQT4),
5. KCNEI (mink syndrome, LQT5),
6. KCNE 2 (LQT6),
7. KCNJ2(LQT7, Andersen’s syndrome) and
8. CACNAIC (LQT8, Timothy syndrome).
42
The long QT in LQTI and LQT2 is caused mostly by T wave lengthening,
whereas in patients with LQT3 lengthening of QT is due to prolongation
of the ST segment.
Certain types of the T and U abnormalities, such as prolonged terminal
portion of T wave down- slope and wide T-U junction, have been seen in
Andersen-Tawil syndrome (LQT7).
43
Hypokalemia
44
45
Hypokalemia has prominent effects on cardiac, skeletal and intestinal
muscle cells.
Hypokalemia predisposes to digoxin toxicity by a number of mechanisms,
including reduced competition between K+ and digoxin for shared binding
sites on cardiac Na+/K+-ATPase subunits.
ECG changes in hypokalemia include broad flat T waves, ST depression,
U waves, and QT prolongation which are most marked when serum K+ is
<2.5 mmol/L.
Hypokalemia also results in hyperpolarization of skeletal muscle,
impairing the capacity to depolarize and contract; resulting in weakness
and even paralysis.
It also causes a skeletal myopathy and predisposes to rhabdomyolysis.
Finally, the paralytic effects of hypokalemia on intestinal smooth muscle
results in intestinal ileus.
The effects of hypokalemia on the kidney can include Na+, Cl– and
HCO3– retention, polyuria, phosphaturia, hypocitraturia, and an activation
of renal ammoniagenesis.
Bicarbonate retention and other acid-base effects of hypokalemia can
contribute to metabolic alkalosis.
46
Hypokalemic polyuria is due to a combination of central polydipsia and an
ADH-resistant renal concentrating defect.
Structural changes in the kidney due to hypokalemia include a relatively
specific injury to proximal tubular cells, interstitial nephritis and renal
cysts.
Hypokalemia also predisposes to AKI and can lead to end-stage renal
disease in patients with long- standing hypokalemia due to eating disorders
and/or laxative abuse.
Hypokalemia and/or reduced dietary K+ are involved in the
pathophysiology and progression of hypertension, heart failure and stroke.
Correction of hypokalemia is important in hypertensive patients treated
with diuretics, in whom BP improves with the establishment of
normokalemia.
The goals of therapy in hypokalemia are to prevent life-threatening
consequences, to replace the associated K+ deficit, and to correct the
underlying cause and/or mitigate future hypokalemia.
The urgency of therapy depends on the severity of hypokalemia, associated
clinical factors and the rate of decline in serum K+.
47
Patients with a prolonged QT interval and other risk factors for arrhythmia
should be monitored during repletion.
Urgent and cautious K+ replacement should be considered, in patients with
severe redistributive hypokalemia (plasma K+ concentration < 2.5mmol/l),
or when serious complications occur.
When sympathetic nervous system is thought to result in redistributive
hypokalemia, as in theophylline overdose, and head injury, high-dose
propranolol (3 mg/kg) should be considered; as this nonspecific -
adrenergic blocker will correct hypokalemia, without the risk of rebound
Oral replacement with KCl is the mainstay of therapy in hypokalemia.
Potassium phosphate, oral or IV, may be used in patients with combined
hypokalemia and hypophosphatemia.
Potassium bicarbonate or potassium citrate should be considered in
patients with hypokalemia and metabolic acidosis.
Hypomagnesemic patients are refractory to K+ replacement alone, such
that concomitant Mg2+ deficiency should always be corrected with oral or
intravenous repletion.
48
In the absence of abnormal K+ redistribution, the total deficit relates to
serum K+, such that serum K+ drops by approximately 0.27 mM for every
100-mmol reduction in total-body stores.
Loss of 400–800 mmol of total-body K+, results in a reduction in serum
K+ by approximately 2.0 mM.
This deficit must be replaced gradually over 24-48 h, with frequent
monitoring of plasma K+ concentration to avoid transient overrepletion
and rebound hyperkalemia.
The use of i.v. administration should be limited to patients unable to use
the enteral route or in the setting of severe complications like paralysis and
arrhythmia.
Intravenous KCl should always be administered in saline containing
solutions, rather than dextrose, because the dextrose-induced increase in
insulin can acutely exacerbate the hypokalemia.
The peripheral intravenous dose is usually 20–40 mmol of KCl per liter,
because higher concentrations can cause local pain from chemical
phlebitis, irritation, and/or sclerosis.
If hypokalemia is severe (<2.5 mmol/L) or critically symptomatic, intravenous KCl can be administered through a central vein, with cardiac monitoring in an ICU setting, at rates of 10–20 mmol/h.
49
Higher rates should be administered for acutely life-threatening
complications.
The absolute amount of administered K+ should be restricted, to about 20
mmol in 100 mL of saline solution, to prevent inadvertent infusion of a
large dose.
Femoral veins are preferable, because i.v. infusion through IJV or
subclavian central lines can acutely increase the local concentration of K+
and hence, affect cardiac conduction.
Strategies to minimize K+ losses should also be considered including,
1. minimizing the dose of non-K+ sparing diuretics,
2. restricting Na+ intake,
3. using clinically appropriate combinations of non-K+-sparing and K+-
sparing medications like e.g., loop diuretics with angiotensin-converting
enzyme inhibitors.
50
Metabolic Acidosis
Metabolic acidosis is defined as, a low arterial blood pH in association with
− a reduced serum HCO3 .
Respiratory compensation results in a decrease in arterial carbon dioxide
tension i.e., PaCO2.
− A low Sr. HCO3 alone is not diagnostic of metabolic acidosis, because it
also results from, renal compensation to chronic respiratory alkalosis.
Measurement of the arterial pH differentiates between these two entities.
After the diagnosis of metabolic acidosis is made, the first step in the
evaluation of the patient is to calculate the serum anion gap.
Anion is the difference between the plasma concentrations of the major
cation, sodium ([Na+]), and the major measured anions, chloride and
bicarbonate ([Cl−] and [HCO3−]), given by the following formula,
+ − − Anion gap = [Na ] − ([Cl ] + [HCO3 ])
51
Causes of Metabolic Acidosis
52
53
Hypocalcemia
The causes of hypocalcemia can be differentiated based to whether serum
PTH levels are low i.e., hypoparathyroidism or high i.e., secondary
hyperparathyroidism.
Impaired PTH production and impaired vitamin D production are the most
common cause of hypocalcemia.
PTH is the only defence against hypocalcemia, and hence,
disorders associated with deficient PTH production may be associated with
profound hypocalcemia.
Hypoparathyroidism commonly results from, inadvertent damage to all
four glands during thyroidectomy or parathyroid gland surgeries.
Hypoparathyroidism can also be seen in autoimmune endocrinopathies.
Hypocalcemia may be associated with infiltrative diseases like sarcoidosis.
Impaired PTH secretion may be secondary to magnesium deficiency or due
to activating mutations in the CaSR or in the G-proteins that mediate CaSR
signals.
Vitamin D deficiency, impaired 1,25(OH)2VIT D production or vitamin D
resistance also cause hypocalcemia.
54
Hypocalcemia in these disorders, is not like that seen with
hypoparathyroidism because the parathyroid glands are able to mount a
compensatory increase in PTH secretion.
Hypocalcemia may also occur, in conditions associated with severe tissue
injury like burns, rhabdomyolysis, tumor lysis syndrome or pancreatitis.
The cause of hypocalcemia includes, a combination of low albumin,
hyperphosphatemia, tissue deposition of Ca and impaired PTH secretion.
Patients with hypocalcemia may be asymptomatic, if the decrease in serum
Ca is relatively mild and chronic but they may present, with life-
threatening complications.
Moderate to severe hypocalcemia is associated with paraesthesia, usually
of the fingers, toes, and circumoral regions which is caused by increased
neuromuscular irritation.
On examination, a Chvostek’s sign i.e., twitching of the circumoral
muscles in response to gentle tapping of the facial nerve just anterior to the
ear may be seen, although it is also seen in normal individuals.
Carpal spasm may be induced by inflation of a blood pressure cuff to 20
mmHg above the patient’s systolic blood pressure for 3 min i.e.,
Trousseau’s sign.
55
Severe hypocalcemia can cause, seizures, carpopedal spasm,
bronchospasm, laryngospasm and a prolonged QT interval.
Evaluation of a patient with hypocalcemia includes measurement of,
1. Sr. calcium,
2. Sr. albumin,
3. Sr. phosphorus,
4. Sr. magnesium, and
5. Sr. PTH level.
A suppressed PTH level in the setting of hypocalcemia establishes,
hypoparathyroidism as the cause of the hypocalcemia.
Elevated PTH level i.e., secondary hyper-parathyroidism, should direct
attention to the vitamin D deficiency as the cause of hypocalcemia.
Vitamin D deficiency is identified by, measuring serum 25-
hydroxyvitamin D levels, which reflects vitamin D stores.
In the setting of renal insufficiency or vitamin D resistance, Sr. 1,25(OH)2
VIT D levels are informative.
56
The treatment depends on the severity of the hypocalcemia and the rapidity
with which hypocalcemia occurs, and the associated complications like,
seizures and laryngospasm.
Acute or symptomatic hypocalcemia is managed with calcium gluconate,
10 mL 10% wt/vol given i.v. diluted in 50 mL of 5% dextrose or 0.9%
sodium chloride, given intravenously over 10 min.
If hypocalcemia persists, it often requires a constant i.v. infusion, typically
10 ampules of calcium gluconate, or 900 mg of calcium in 1 L of 5%
dextrose or 0.9% sodium chloride, being administered over 24 h.
Hypomagnesemia, if it is present, should be treated with appropriate Mg
supplementation.
Chronic hypocalcemia due to hypoparathyroidism is treated with calcium
supplements i.e., 1000–1500 mg/d elemental calcium in divided doses and
either vitamin D2 or D3 i.e., 25,000–100,000 U/day or calcitriol
i.e.,1,25(OH)2D, 0.25–2 μg/day.
Other vitamin D metabolites like, dihydrotachysterol, alfacalcidiol are not
used nowadays.
57
Vitamin D deficiency, however, is treated best using vitamin D
supplementation, generally responds to low doses of vitamin D i.e., 50,000
U, 2–3 times per week for several months.
Vitamin D deficiency due to malabsorption may require much higher doses
i.e., 100,000 U/d or higher.
The treatment goal, is to bring serum calcium into the low normal range
and to avoid hypercalciuria as it may lead on to nephrolithiasis.
58
59
MATERIALS AND METHODS
STUDY POPULATION
The study will be conducted on 50 patients admitted to Government
Rajaji Hospital & Madurai Medical College during the study period from
February 2019 to July 2019.
INCLUSION CRITERIA
Patients with history of Cleistanthus collinus poisoning within 48hrs.
EXCLUSION CRITERIA
Age < 18 years
Drug history- Quinidine, procainamide, TCA’s, bisphosphonates
Chronic kidney disease
Acute pancreatitis
Acute myocardial infarction
Advanced or complete AV block
60
ANTICIPATED OUTCOME
Increased incidence of mortality in Cleistanthus collinus poisoning patients with prolonged QTc interval.
DATA COLLECTION
Informed consent will be obtained from all patients to be enrolled for the study. In all the patients, relevant information will be collected in a predesigned proforma.
The patients are selected based on history, ECG and biochemical tests.
The incidence of QTc prolongation is assessed. In those with prolonged QTc interval, the outcome is assessed in the form of mortality or discharge from the hospital.
LABORATORY INVESTIGATIONS
Complete blood count
Blood sugar test.
Renal function test
Liver function test
Sr. electrolytes
Sr. amylase
Sr. Calcium
Electrocardiography
61
DESIGN OF STUDY
Prospective study.
PERIOD OF STUDY
6 MONTHS (February 2019 to July 2019)
COLLABORATING DEPARTMENTS:
DEPARTMENT OF BIOCHEMISTRY
ETHICAL CLEARANCE: Applied for
CONSENT: Individual written and informed consent
ANALYSIS: Statistical analysis will be performed using appropriate tests required according to data
CONFLICT OF INTEREST: Nil
FINANCIAL SUPPORT: Self
PARTICIPANTS: 50 Cleistanthus collinus poisoning patients at Government
Rajaji Hospital, Madurai
62
OBSERVATION
Statistical analysis
Statistical analysis was done using SPSS version 16(SPSS Inc., Chicago,
IL).
The results were presented as mean, Standard error and Standard deviation
for continuous data and as percentages for categorical data.
Distribution of the computed data was analysed using shapirowilks test.
The clinical, laboratory variables were compared among survivors and
expired in the study population.
Comparisons of the continuous data between the groups were performed
by Student’s t-test.
Qualitative differences between the groups were analyzed by the Chi-
square test or Fisher’s exact test.
A p-value < 0.05 were considered to indicate statistical significance.
63
RESULTS
Distribution of clinical profile and laboratory profile among study population
Std. Variables Mean Minimum Maximum Median IQR Deviation
Age in yrs 27.22 6.42 18 41 26 9.25
Serum calcium 9.236 0.75 7.4 10.6 9.25 0.72
Serum potassium 3.576 0.70 1.6 4.7 3.6 0.7
QTc interval 424.6 35.29 380 510 420 0
Serum pH 7.36 0.54 7.24 7.49 7.365 0.8
Mean distribution of age and laboratory profile among study population 30 27.22
25
20 Age in yrs
15 Serum calcium Serum potassium
10 9.236 Serum pH 7.36
5 3.576
0 Age in yrs Serum calcium Serum potassium Serum pH
64
Comparison of the laboratory profile and clinical profile among expired and survivors of the study population
Survivors (N=44) Expired (N=6)
Std. Std. Error Std. Std. Error p Mean Mean Deviation Mean Deviation Mean value
Age in years 27.05 6.23 0.94 28.5 8.26 3.374 0.608 0.001* serum calcium 9.42 0.548 0.082 7.85 0.59 0.24 * serum 0.001* 3.74 0.51 0.078 2.33 0.63 0.25 potassium * 0.001* QTc interval 415.68 25.73 3.88 490 26.077 10.64 * 0.001* serum pH 7.37 0.04 0.006 7.26 0.01 0.007 * Student t test; **shows (p<0.001)
Comparison of the laboratory profile among expired and survivors of the study population
28.5 30 27.05
25
20
15 Survivors 9.42 Expired 10 7.85 7.26 7.37
3.74 5 2.33
0 Age in years serum calcium serum serum pH potassium
65
QTc interval
Comparison of QTc interval among expired and survivors of the study population
490 500
480
460 Survivors 440 415.68 Expired 420
400
380
360 Survivors Expired
The average QTc interval among survivors is 415 msec.
The average QTc interval among expired is 490 msec.
The QTc interval significantly identifies patients with a high chance of
poor outcomes.
The significance of QTc is explained by the hypokalemia and
hypocalcemia caused by toxic effects of the plant.
66
Age Distribution
Comparison of age among expired and survivors of the study population
28.5
28.5
28
27.5 Survivors 27.05 Expired 27
26.5
26 Survivors Expired
The incidence of Cleistanthus collinus poisoning is significantly higher in
younger age groups.
It is due to the ease of availability.
The plant is seen all over southern states of the nation.
67
Serum Calcium
Comparison of serum calcium among expired and survivors of the study population
9.42 10 9 7.85 8 7 Survivors 6 5 Expired 4 3 2 1 0 Survivors Expired
Serum calcium levels are significantly reduced among expired, as
compared to survivors.
The mean Sr. calcium among expired is 7.85.
It is in part due to renal involvement in patients with Cleistanthus collinus
poisoning.
68
Serum Potassium
Comparison of serum potassium among expired and survivors of the study population
3.74 4 3.5
3 2.33 2.5 Survivors 2 Expired 1.5 1 0.5 0 Survivors Expired
Serum potassium is significantly reduced in patients who expired as
compared to survivors.
Even in survivors the serum potassium levels are in the low normal
levels.
The observation is similar to the previous studies.
69
Acid-Base Balance
Comparison of serum pH among expired and survivors of the study population
7.37 7.38
7.36
7.34
7.32 Survivors 7.3 Expired 7.28 7.26
7.26
7.24
7.22
7.2 Survivors Expired
pH is an important prognostic marker in Cleistanthus collinus poisoning.
The mean pH among expired is 7.26.
Hence, ABG is an important initial investigation in assessing prognosis.
70
GENDER DISTRIBUTION
Gender wise distribution among expired and survivors of the study population
Outcome Total Sex Survivors Expired P value
Count (N) 6 1 7 Male
% within sex 85.7% 14.3% 100.0%
Count (N) 38 5 43 0.616 Female % within sex 88.4% 11.6% 100.0%
Fisher's Exact Test; Not significant
Gender wise distribution among expired and survivors of the study population
85.70% 88.40% 90.00% 80.00% 70.00% 60.00% Male 50.00% Female 40.00% 30.00% 14.30% 20.00% 11.60% 10.00% 0.00% Survivors Expired
71
Male
14.30%
Survivors
85.70% Expired
Female
11.60%
Survivors Expired 88.40%
72
Distribution of categorical parameters among the study population
Parameters Frequency (N) Percent (%)
Gender Male 7 14
female 43 86
ST-T interval Abnormal 41 82
normal 9 18
Dyspnoea Absent 46 92
present 4 8
Elevation of present 40 80 SGOT
Absent 10 20
73
Gender Distribution
Genderwise distribution of study population
90%
80%
70%
60% Male 50% female 40%
30%
20%
10%
0% Male female
The consumption of Cleistanthus collinus is very high among females as
compared to males.
It is attributable to easy availability.
74
ECG – ST-T Changes
Distribution of ST-T interval among study population
90% 82% 80% 70% 60% 50% ST-T interval Abnormal 40% ST-T interval normal 30% 18% 20% 10% 0% Abnormal normal ST-T interval
Comparison of ST-T changes among expired and survivors
90.00% 84.10%
80.00% 66.70% 70.00% 60.00%
50.00% ST-T changes normal ST-T changes Abnormal 40.00% 33.30%
30.00% 15.90% 20.00%
10.00%
0.00% Expired survivors
75
Dyspnoea
Comparision of dyspnea among expired and survivors
100.00% 100.00% 90.00% 80.00% 66.70% 70.00%
60.00% Dyspnea present 50.00% Dyspnea Absent 33.30% 40.00% 30.00% 20.00% 10.00% 0 0.00% Expired Survivors
The incidence of dyspnoea among survivors is 0% and 66% among
expired.
The presence of dyspnoea is a very specific marker of mortality in
patients with Cleistanthus collinus poisoning.
It per se indicates that the patient has underlying metabolic acidosis.
76
Liver Enzymes
Distribution of elevation of SGOTamong study population
80% 80%
70%
60%
50% Elevation of SGOT present 40% Elevation of SGOT Absent 30% 20% 20%
10%
0% present Absent Elevation of SGOT
Comparison of SGOT changes among expired and survivors
90.00% 83.30% 79.50% 80.00%
70.00%
60.00% elevation_of_SGOT>40 normal 50.00%
40.00% elevation_of_SGOT>40 Abnormal 30.00% 20.50% 16.70% 20.00%
10.00%
0.00% Expired survivors
77
Comparison of categorical variables among expired and survivors of the study population
Outcome
Expired Survivors
(N=6) (N=44) p value
Count 2 44 Absent % within outcome 33.3% 100.00% 0.001* Dyspnoea Count 4 0 present % within outcome 66.7% 0%
Count 4 37 0.293 Abnormal ST-T % within outcome 66.70% 84.10%
changes Count 2 7 normal % within outcome 33.30% 15.90%
Count 5 35 Abnormal Elevation of % within outcome 83.30% 79.50% 0.656
SGOT>40 Count 1 9 normal % within outcome 16.70% 20.50%
Fisher's Exact Test; shows *(p<0.05)
78
DISCUSSION
The study is conducted among 50 patients with a history of Cleistanthus
collinus poisoning, who were admitted between Feb 2019 and July 2019 in
Government Rajaji Hospital, Madurai.
Among the expired, the mean age was 28yrs and it was 27yrs among
survivors.
The poisoning was more common among young adults.
The incidence was 6 times more common in females as compared to males.
In the study group, 82% had ST-T changes on ECG. The incidence among
survivors is 66% and among expired, it is 84%.
Hence, ST-T changes were not a significant predictor of mortality in our
study group.
Among the survivors, elevation of SGOT was seen in 79% of individuals
and among expired, the incidence is 83%.
Hence, SGOT was not a significant predictor of mortality in our study
group.
The incidence of dyspnea was 66% in expired group and 0% in the
survivors group.
The results indicate that patients who develop dyspnea at presentation are
more likely to have a poor prognosis.
79
The mean serum calcium among survivors is 9.42 and among expired it is
7.85.
The lower the Sr. calcium, the poorer the prognosis.
The serum potassium levels were significantly reduced among expired
group with a p value < 0.001.
The serum potassium levels were in the low normal range even among
survivors.
The QTc interval among survivors was 415msec and among expired the
mean values is 490msec.
Hence, QTc prolongation is a significant marker of mortality with a p-value
<0.001.
LIMITATIONS
Although the study results were comparable to the previous studies in
Cleistanthus collinus poisoning, the study group was small. Hence, larger
studies may be required in the future.
80
CONCLUSION
The ECG change of QTc prolongation, at 24hrs of presentation, is a reliable and readily available maker of prognosis in patients admitted with Cleistanthus collinus poisoning.
81
ANNEXURE
BIBLIOGRAPHY
1. Subrahmanyam BV, ed. Modi’s Medical Jurisprudence.
2. Toxicology. 22nd edition (student edition); New Delhi, Butterworth’s
India, 2001 :Section2:250-252. Asolkar LV, Kakkar KK, Chakre OJ, eds.
Second Supplement to Glossary of Indian Medicinal Plants with Active
Principles Part-1(A-K) (1965-1981) : New Delhi,National Institute of
Science Communication(CSIR), 2000:214.
3. Maiti PC, Das AK. Chemical examination of the fruits of Cleistanthus
collinus. Curr Sci 1965;34:179-181. Govindachari TR, Sathe SS,
Vishwanathan N, Pai Br, Srinivasan M. Chemical constituents of
Cleistanthus collinus.Tetrahedron1969;24:2815-21.
4. Lakshmi TG, Srimanarayana G, Subba Rao NV. A new glucoside from
Cleistanthus collinus. Curr Sci 1970;39:395-6. Joshi SS, Srivastava RK.
Chemical examination of Cleistanthus collinus seeds. J Oil Technol Assoc
India 1977;9:156-7 Anjaneyulu ASR, Ramaiah PA, Ramachandra Rao l.
Crystalline constituents of Euphorbiaceae; Part XVI A new diphyllin
glycoside from Cleistanthus collinus. Indian J Chem 1977;15B:10-11.
5. Anjaneyulu ASR, Ramaiah PA, Ramachandra Rao L. New lignans from
the heartwood of Cleistanthus collinus. Tetrahedron 1981;37:3641-
52. Satyanarayana P, Subrahmanyam P, Koteswara RP. Chemical
constituents of Cleistanthus collinus roots. Indian J Pharm Sci 1984;46:95-
96. 6. Rajagopal Naidu S,Venkat Rao P, Subrahmanyam CA. The microscopy
and chemistry of oduvin. J Proc Inst Chem India 1944;16:59-63. Kurien
T, Dayal AK, Gijsbers A, Seshadri MB, Cherian AM. Oduvanthalai leaf
poisoning. J Assoc Physicians India 1985;35:769-71.
7. Nagaraj S. Cardiac toxicity of oduvanthalai (Cleistanthus collinus)
common leaves poisoning in Tamil nadu. (Report of 25 cases). The
Antiseptic 1987:33-35. Das AK. Venkatadri Clinical profile of
Oduvanthalai poisoning.M.D. dissertation submitted to Pondicherry
University by Dr.Venkatadri, 1989.
8. Anapoorani KS. Analytical biochemistry in forensic sciences:
Toxicological aspects of Cleistanthus collinus. A PhD thesis submitted to
the University of Madras, 1985. Kanthasamy A, Govindasamy S,
Damodaran C. Novel inhibition of LDH isoenzymes by Cleistanthus
collinus toxins. Curr Sci 1986;55:854-56.
9. Ragupathi G, Prabhasankar P, Chandrasekharan P, Annapoorani KS,
Damodaran C. Enzyme linked immunosorbent assay for the phytotoxin
Cleistanthin A. J Immunoassay 1992;13:3221-338.
10. Annapoorani KS, Damodaran C, Chandrasekharan P. High- pressure liquid
chromatography separation of arylnaphthalene lignan lactones. J Liq
Chromatogr 1985;8:1173-94.
11. Annapoorani KS, Periakali P, Ilangovan S, Damodaran C,
Chandrasekharan P. Spectrofluorometric determination of the toxic
constituents of Cleistanthus collinus. J Anal Toxicol 1984;8:182-186.
12. Annapoorani KS, Damodaran C, Chandrasekharan P. Solid - state
fluorodensitometric quantitation of arylnaphthalene lignan lactones of
Cleistanthus collinus. J Chromatogr 1984;303;296-305.
13. Anapoorani KS, Damodaran C, Chandrasekharan P. A promising antidote
to Cleistanthus collinus poisoning. J Sci Soc Ind 1986;2:3-6.
PROFORMA
Name: Age / Sex: Occupation: Presenting complaints:
H/O Cleistanthus collinus poisoning in the past 48hrs.
Past History: H/o DM, HT, CKD, CVD, DRUG INTAKE, CAD, Alcohol intake
Clinical Examination:
General Examination: Consciousness, Pallor, Jaundice, Clubbing, Lymphadenopathy, Hydration status
Vitals: PR BP RR SpO2 Systemic examination:
CVS:
RS:
ABDOMEN:
CNS:
Laboratory investigations:
a) Complete blood count b) Blood sugar test. c) Renal function test d) Liver function test e) Sr. electrolytes f) Sr. amylase g) Sr. Calcium h) Electrocardiography
ABBREVIATIONS
QTc - Corrected QT interval.
SpO2 - Oxygen Saturation by Pulse oximetry.
BP - Blood pressure.
MASTER CHART
sr.Ca sr.K elevation QTc ST-T serum sr.no age sex at 24 at 24 outcome dysnoea of SGOT interval changes pH hrs hrs >40 1 21 f 10.3 3.7 390 A N N 7.38 N 2 30 f 10.6 3.4 410 A N N 7.35 N 3 26 f 9.2 3.9 380 A N N 7.41 N 4 29 f 9.6 3.5 440 A N N 7.36 N 5 18 f 9.5 4.1 390 A N N 7.4 N 6 24 f 9.3 3.3 440 A N N 7.32 N 7 32 f 9.9 4.3 400 A Y N 7.42 Y 8 36 m 9.4 3.8 420 A N Y 7.45 N 9 22 f 10.1 4.4 380 A Y N 7.37 N 10 26 f 9 3.2 440 E N N 7.28 N 11 26 f 9.8 2.5 460 A Y N 7.38 N 12 29 m 7.8 3.5 420 A N Y 7.34 Y 13 19 f 9.2 3.6 450 A N N 7.36 N 14 31 f 9.7 4 400 A N N 7.39 N 15 40 f 10.3 3.8 390 A N N 7.44 N 16 22 m 9.4 4.1 420 A N N 7.35 Y 17 25 f 7.6 1.9 500 E Y N 7.26 N 18 21 f 9.1 3.6 420 A N N 7.37 N 19 28 f 9.9 4.2 390 A N N 7.4 N 20 33 f 8.1 3.4 440 A N Y 7.42 N 21 25 f 9.4 4.6 400 A N N 7.36 Y 22 29 f 9.1 3.5 430 A Y N 7.43 N 23 20 f 8.9 3.2 440 A N N 7.37 N 24 18 f 9.2 4.7 400 A N Y 7.34 N 25 35 f 9.9 3.6 430 A Y N 7.49 Y 26 19 m 10.1 3.1 440 A N N 7.42 N 27 25 f 7.4 2.2 490 E N N 7.29 N 28 28 f 9 3.8 420 A Y N 7.33 N 29 19 f 9.7 3 410 A N N 7.39 N 30 31 f 9.2 3.7 430 A N N 7.37 N 31 23 f 9.1 4.2 410 A N N 7.34 Y 32 27 f 10.2 3.4 450 A N N 7.32 Y 33 18 m 7.8 3 510 E N N 7.26 N 34 37 f 9.1 3.3 480 A N N 7.41 N 35 30 f 9.3 4.2 420 A Y N 7.45 N 36 21 f 8.9 4.5 390 A N N 7.37 N 37 26 f 9.6 3.5 430 A N N 7.34 N 38 28 m 9.1 4.7 420 A N N 7.41 N 39 38 f 7.4 2.1 490 E Y N 7.24 Y 40 26 f 9.2 4.2 380 A N N 7.36 N 41 41 f 9.5 3.8 400 A N N 7.32 N 42 29 f 9.1 3.6 410 A N N 7.36 Y 43 23 f 9.7 3.3 420 A N N 7.39 N 44 28 f 8.8 3.7 400 A N N 7.33 N 45 21 f 9.5 4.1 380 A N N 7.42 N 46 25 m 8.9 2.3 480 A N N 7.3 N 47 20 f 9.9 3.6 410 A N N 7.29 N 48 33 f 9.1 3.9 390 A N N 7.36 Y 49 41 f 10 4.2 380 A N N 7.41 N 50 39 f 7.9 1.6 510 E N N 7.27 N
ETHICAL COMMITTEE APPROVAL LETTER
ANTI PLAGIARISM CERTIFICATE
CERTIFICATE
This is to certify that this dissertation titled “QTc prolongation as a prognostic marker in Cleistanthus collinus poisoning” of the candidate
Dr. G. SHANTHOSH, with registration number 201711119 for the award of
M.D degree in the branch of GENERAL MEDICINE. I personally verified the urkund.com website for the purpose of plagiarism check. I found that the uploaded thesis file contains from introduction to conclusion pages and result shows 6 percentage of plagiarism in the dissertation.
Guide and supervisor sign and seal