tetanus article ijccm
TRANSCRIPT
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TITLE PAGE
WORD COUNT FOR ABSTRACT- 250
WORD COUNT FOR TEXT- 2871 ( Including Introduction, Material and Methods,
Results, Conclusions, Aknowledgements, References)
CORRESPONDING AUTHOR- Professor (Dr) Nilkanth T. Awad, M.D,
Head of Department of Pulmonary Medicine, L.T.M.M.C & L.T.M.G.H, Sion,
Mumbai-22
ADDRESS-
TEL NO- 02224044644
FAX- 02224044644
EMAIL [email protected]
Co-author- Dr. Unnati D. Desai, M.D,
Registrar, Department of Pulmonary Medicine, L.T.M.M.C & L.T.M.G.H, Sion,
Mumbai-22
ADDRESS-
TEL NO-02224044644
FAX- 02224044644
EMAIL- [email protected]
For both authors there are no conflicts of interest , no financial disclosures, funded
by none
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ABSTRACT PAGE
TITLE MANAGEMENT OF TETANUS IN INTENSIVE RESPIRATORY CARE UNIT
- OUTCOME WITH MAGNESIUM SULPHATE
ABSTRACT-
Background and Aims- Tetanus is not eradicated in developing world. Standard
tetanus treatment consists of sedation, prompt ventilation, paralytics, treating
autonomic dysfunction, antibiotics, immunoglobulin. We studied newer adjunctive
medication, intravenous magnesium sulphate in outcome of tetanus and parameters
affecting outcome.
Subjects and Methods-Ours is an observational study in 61 patients admitted to
tertiary hospital intensive respiratory care unit. After noting vitals intrathecal tetanus
immunoglobulin, antibiotics, oral diazepam and need based intravenous sedation
and paralysis were given. A subset received magnesium sulphate. Outcome was
discharge or death.24 received magnesium sulphate with diazepam. 37 received
only diazepam
Results- 93.40% were males, 57%unskilled labourers. 7 (11.5%) were earlier
immunised. In 28(45.9%) incubation period was unknown. 45(73.8%) had period of
onset within 2 days. Mean diazepam dose in those received magnesium sulphate
was 6898.33mg and not received was 9147.10mg. Severe group mean diazepam
dose was 6562.50mg in those receiving and 11236.92mg in not receiving
magnesium sulphate. Mild tetanus required 364.67gm magnesium sulphate and
severe 546.67gm. Of 55(90%) tracheostomised 39(71%) tracheostomised by 2 days.
Mean total stay was 26.75 days in those receiving magnesium sulphate; in others
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29.11 days, increasing to 33.83(+/-11.8) days in very severe. 28(46%) required
ventilator. Overall death 24.5%. 4 deaths (16.7%) occurred in 24 patients receiving
magnesium sulphate while 11(29.7%) deaths in 37 not receiving. 8 discharged of 12
ventilated receiving magnesium sulphate. 6 discharged of 16 ventilated not receiving
magnesium sulphate.
Conclusion-Magnesium sulphate did not influence need for tracheostomy, ventilator,
stay and mortality except decreased sedative dosage in severe tetanus.
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TEXT
INTRODUCTION-
Tetanus is important cause of hospital admission and deaths in developing world,
characterized by prolonged, lock jaw, muscle spasms, sometimes autonomic
instability. Antitoxin, antibiotics improve outcome but optimum management of
respiratory compromise that characterize severe form remains uncertain.
Supportive management aims at controlling muscle spasms, maintaining patent
upper airway, providing adequate ventilation, treating autonomic complications.
Benzodiazepines in high doses are mainstay for relaxing muscles and controlling
spasms. Severe spasms require nondepolarizing neuromuscular agents. Magnesium
sulphate is nowadays used for control of spasms and autonomic dysfunction.
In this observational study clinical course, effect, outcome of tetanus patients
referred to a tertiary hospital by using magnesium sulphate and sedatives vs only
sedation in controlling spasms, autonomic instability and need for sedation and
paralytics was studied.
MATERIAL AND METHODS-
The study was conducted in intensive respiratory care unit of tertiary university
hospital after IRB approval (IEC-HR/DISS/94(11/07) IEC, L.T.M.GENERAL
HOSPITAL). Tetanus patients above 12 years of age, admitted from January 2004 to
September 2009 were enrolled. All patients presenting to casualty with acute onset
generalized muscle spasms, rigidity, ophisthotonus, trismus, spatula test positive
leading to clinical diagnosis of tetanus were included in the study. Pulse,Blood
Pressure, Respiratory Rate, Temperature recorded, General and Systemic
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Examination done. Abletts score was used to grade tetanus severity. Patients with
drug poisoning, seizures, meningitis, encephalitis, dental pathology, hypocalcemic
tetany, papilloedema were excluded.
Patients were kept in calm atmosphere without external stimulus, oxygen
administered if required, antibiotics Ciprofloxacin, Metronidazole, antihelminthics
given, injection Tetanus Toxoid given intramuscularly, oral diazepam given through
Ryles tube. Intravenous sedatives and paralytics given if needed. Intravenous
magnesium sulphate was given in a subset of patients comparing previous without
magnesium sulphate.
Patients on magnesium sulphate were monitored with electrocardiogram, knee jerk
suppression, Chvostek sign, Trousseau sign, respiratory depression, serum calcium.
Oral and intravenous calcium was supplemented.
Tracheostomy was done if conducted sounds, secretions, laryngospasm causing
desaturation < 90% and finally on physicians opinion.
Patients were ventilated with mechanical ventilator if uncontrolled spasms caused
respiratory failure and if spasm control required paralytics on top of sedatives and
baclofen. Complete hemogram, renal and liver function tests, random blood sugar,
serum calcium, Chest X ray, electrocardiogram, Cerebrospinal fluid, Urine for
myoglobinuria were done.
Outcome measured as discharge from hospital or death.
Statistical Analysis done using the chi square test, Annova test.
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RESULTS-
61 patients were studied. 24 received magnesium sulphate and sedatives, 37
without magnesium sulphate. Their age groups ranged from 14 to 80 years. Mean
age 29.67 years. Distribution is as in table 1.
Outcome Total
Discharge Death
Age
group
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51+ 5 1 6
Total 46 15 61
Table1
57(93.4%) were males, 4(6.6%) females.
Cases with mild severity were 5, moderate 12, severe 21, very severe 23.
Distribution is as in table 2
Receivedmagnesiumsulphate Total
Yes No
Ablettsscore
Mild Count 3 2 5
% 12.5% 5.4% 8.2%
Moderate Count 6 6 12
% 25.0% 16.2% 19.7%
Severe Count 6 15 21
% 25.0% 40.5% 34.4%
VerySevere
Count 9 14 23
% 37.5% 37.8% 37.7%
Total Count 24 37 61
% 100.0% 100.0% 100.0%
Table 2
As severity increased more deaths were observed. It was statistically significant.
( Chi-Square Test p= 0.010 ).15 deaths occurred in the study. 4 deaths(16.7%)
occured in 24 patients receiving magnesium sulphate, all in the very severe group.
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11 deaths occured in 37(29.7%) not receiving magnesium sulphate, 1death in
moderate, 3 in severe and 7 in very severe group.Though not statistically significant
there was increase in total deaths in patients not receiving magnesium sulphate.
Outcome in each group is as in table 3
Abletts score Received magnesium sulphate Outcome Total
discharge Death
Mild Yes 3 0 3
No 2 0 2
Total 5 0 5
Moderate Yes 6 0 6
No 5 1 6
Total 11 1 12
Severe Yes 6 0 6
No 12 3 15
Total 18 3 21
Very Severe Yes 5 4 9
No 7 7 14
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Total 12 11 23
Table 3
Nine patients died due to sepsis , one died due to ARDS, one due to autonomic
dysfunction, one due to cardiac arrest, in three the cause was unknown.
7 received injection tetanus toxoid in past. Immunisation rate was 11.5%. Everyone
received tetanus toxoid after admission.
Incubation period was unknown in 28 (45.9%).In others it ranged from 2 to 90 days.
Mean period of onset was 2.38 days, ranging from 1 to 10 days. In 45( 73.8%)
patients it was within 48 hours. As the period of onset increased disease severity
decreased significantly ( chi square , p= 0.006).
55 patients required tracheostomy. As severity increased need for trachoestomy
increased and was statistically significant (table4)
Abletts score
Mild Moderate Severe Very Severe
Tracheo-
stomy
NO 5 1 0 0
YES 0 11 21 23
Table 4 Chi-Square Tests p=0.000
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Patients tracheostomised earlier on admission had significantly severe disease .
Tracheostomy was required for minimum 7 to maximum 47 days in surviving
patients. Mean 20.41 days
6 did not require tracheostomy and 2 patients data on day of tracheostomy was
unavailable.
60 received diazepam. 5 patients data on diazepam required was insufficient. Mean
diazepam dose received was 8165.82mg. In patients receiving magnesium sulphate
it was 6898.33mg.In patients not receiving magnesium sulphate it was 9147.10mg.
As severity increased mean diazepam dose increased and was statistically
significant (table 5) ANOVA test p= 0.025
Abletts score
Mean diazepam
(mg) N
Mild 690.00 4
Moderate 3351.25 12
Severe 9760.79 19
Very Severe 11034.50 20
Total 8165.82 55
Table 5
Maximum total diazepam required was 39810mg and minimum total dose of
180mg.Average diazepam dose ranged from 81mg to 1440mg/day. Mean diazepam
dose was 6562.50mg in patients receiving and 11236.92mg in patients not receiving
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magnesium sulphate in severe group. In other groups there was no difference
(table6)
Abletts score Received magnesium sulphate Mean diazepam (mg)
Mild Yes 676.67
No 730.00
Moderate Yes 3367.50
No 3335.00
Severe Yes 6562.50
No 11236.9
Very Severe Yes 11550.0
No 10612.7
Table 6
24 patients received magnesium sulphate for minimum 2 to maximum 13 days.
Mean for 9 days. Mean magnesium sulphate dose increased with severity, was
statistically significant p=0.047(Anova test) (table 7). Three patients in very severe
group received low doses of magnesium sulphate due to severe hypocalcemia
inspite of calcium supplementation
Abletts score Mean magnesium sulphate dose ( gms)
Mild 364.67
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Moderate 325.67
Severe 548.67
Very Severe 272.22
Total 366.25
Table-7
33 did not require ventilator and 28 required ventilator. Ventilated patients consisted
of 1 in moderate, 9 in severe, 18 in very severe group. Ventilated group had more
deaths, was statistically significant (table8). 12 of 24 receiving magnesium sulphate
and 16 of 37 not receiving required ventilation.
outcome Total
discharge Death
Ventilation NO Count 32 1 33
YES Count 14 14 28
Total Count 46 15 61
Table 8 Chi-square test, p= 0.000,
In ventilated patients receiving magnesium sulphate in severe group 4 discharged
,none died. Very severe 4 died and 4 discharged. Whereas ventilated patients not
receiving magnesium sulphate in moderate group one died,in severe 3 discharged
and 2 died,in very severe 3 discharged and 7 died.
In survived, total stay ranged from minimum 7 to maximum 64 days. As severity
increased, stay increased, was statistically significant ANOVA test, p=0.003. Mean
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stay in those receiving magnesium sulphate was 26.75 days and those not receiving
was 29.11 days.
Hypocalcemia occurred in 20 patients receiving magnesium sulphate.Two patients
on magnesium sulphate therapy had apneas and required short term ventilation for
same.
DISCUSSION-
In present study majority are young mean age being 29.67 years. In Thwaites study
it was 47 years (1). Present study had 57(93.4%) males and 4 females. This could
be due to higher exposure to injuries in men. In studies conducted by Edmonson( 4),
Onwuchekwa(2) , Thwaites(1) males were 75% , 58.1% and 72% respectively.
In present study 57% patients were unskilled labourers , 20% skilled labourers , 7%
farmers , 7% students , 1.5% civil servant , 4.5% traders , 3% unemployed. In
Onwuchekwas study 6% were unskilled labourers , 26% skilled labourers , 4%
farmers , 26% students , 18% civil servants , 6% traders , unemployed 6% ( 2 ).
Unskilled labourers are at increased risk of tetanus in our study followed by skilled
labourers. Onwuchekwas study reveals similar results except skilled labourers and
students in their study were at higher risk to develop tetanus, probably due to
ignorance of immunisation( 2 ).
All patients in our study received intrathecal tetanus immunoglobulin. Geetas study
states it reduces mortality, morbidity, in mild and moderate tetanus( 5 ). Agarwal
states in mild tetanus it reduces mortality, retards progression of disease ,reduces
stay, need for tracheostomy, sedative dose in mild tetanus( 6 ). Kabura concluded
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that intrathecal administration of TIG is more beneficial than intramuscular
administration(7 ).
Only 7 (11.5%) of 61 were earlier immunised. In Lees study 20% and Pawars study
4.2% received tetanus toxoid in past(8)(9). In study from kasturba hospital 20% were
previously immunised(10). This is more or less common in Indian studies.
In 28(45.9%) incubation period was unknown as history of antecedent event was not
elicited. In Edmonsons study it was unknown in 45%(4).
In 73.8% the period of onset was within 48 hours and more than 48 hours in 26.2%.
In Onwuchekwas study period of onset was within 48 hours in 41.9% and more than
48 hours in 58.1%(1) . In L.Ramchandra s study 60% had period of onset within 48
hrs (10). In this study of the 15 deaths, all had period of onset within 3 days and 13
within 2 days. As period of onset increased, severity decreased and mortality
decreased, is established in the universally accepted Gallais score( 11 ). Mortality
was 87% in patients having period of onset within 48 hours in current study . In
Yodh s study it was 61.1%(12) and in Bhatts study 65.5%( 13).
Various scores are used to grade severity of tetanus. We used the Abletts score
(14). Patel and Joag suggested classifying tetanus cases into five grades( 15 ).
In present study 5(8.2%) belonged to mild, 12(19.7%) to moderate, 21(34.4 %) to
severe and 23(37.7%) to very severe group. Edmonsons study distribution in the
mild, moderate, severe, very severe group was 7% , 3% , 69% , 21% respectively(4).
Trujillos study had 13.4% patients in mild, moderate group and 86.6% patients in
severe, very severe group(16).
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Patients tracheostomised earlier on admission had statistically significant severe
disease . Tracheostomy was required for minimum 7 to maximum 47 days in
surviving patients. Mean of 20.41 days. 39 were tracheostomised in first 48 hours
and 14 later on.
Femi- pearse used 2.4 mg/kg/day of diazepam in mild, 4.3 mg/kg/day in moderate
and 9.4 mg/kg/day in severe and very severe tetanus. Maximum diazepam dose
used was 40 mg/kg/day. In present study maximum total diazepam required was
39810mg, minimum total diazepam was180mg.Average diazepam dose ranged from
81mg/day to 1440mg/day in patients not receiving magnesium sulphate,it ranged
from 53 mg/day to 1380 mg/day for patients receiving magnesium sulphate, not
statistically significant.
Mean diazepam dose was 6562.50mg in patients receiving and 11236.92mg in
patients not receiving magnesium sulphate in severe group. In other groups there
was no much difference. In Thwaites study (1) average diazepam dose in mg/kg/day
was 40 and 47.1 in those receiving and not receiving magnesium sulphate
respectively, their average midazolam dose in mg/kg/day was 7.1 and 1.4
respectively. The total sedative dose was 47.1 and 48.5 not showing much
significance. We did not use midazolam.
Present study showed no significant difference in paralytic requirement in patients
receiving and not receiving magnesium sulphate. Thwaites study had significant
decrease in need for paralysis in patients receiving magnesium sulphate. This may
be in contrast because Thwaites probably used more midazolam in addition to
diazepam administration and put more patients(80%) on ventilation. Whereas in our
study only 46% needed ventilation. Of 28 ventilated patients 12 received and 16 did
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11 deaths occurred in 37 patients not receiving magnesium sulphate, 1 in
moderate,3 in severe, 7 in very severe groups. Thwaites reported mortality of 16% in
severe group not receiving magnesium sulphate, our study it was 0% in mild, 2.7% in
moderate,8.1% in severe, 18.9% in very severe group. Death rate in Thwaites study
was confined to only severe group as per Abletts score. Death rate in our study was
confined to very severe group. Though not statistically significant there was increase
in deaths in patients not receiving magnesium sulphate
Thwaites stated, preventilator era deaths in tetanus occurred due to laryngospasm,
asphyxia while now hospital infections and autonomic dysfunction are major causes
of death. In our study 9 of 15 deaths were due to sepsis. Other causes were ARDS ,
autonomic dysfunction , cardiac arrest. Sepsis related deaths are similar to Trujillos
study(16)
Magnesium sulphate infusion led to fall in serum calcium levels below 7mg and
bradycardia. Two in magnesium sulphate group had apneas on magnesium sulphate
and one died due to cardiac arrest.
CONCLUSIONS-
In this study males predominantly affected and unskilled labourers commonest to
suffer.Magnesium sulphate did not influence need for tracheostomy, ventilator, stay
and mortality. Though not significant it showed overall decreased trend for mortality
with magnesium sulphate and decreased sedative dosage in severe tetanus. As
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severity increased dosages of magnesium sulphate and diazepam increased
significantly.
ACKNOWLEDGEMENTS-
Both authors have no conflicts of interest. Funded by none, financial disclosure
none. This study is done under personal and close supervision of
Professor(Dr.)N.T.Awad and data collection, analysis done by Dr.Unnati Desai. We
thank the Dean of L.T.M.Medical College for permission and other staff members
involved in management of tetanus patients in IRCU.
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randomised control trial Lancet 2006;368:1436-43
2.Onwuchekwa et al A 10 year review of outcome of management of tetanus in
adults in Nigerian tertiary hospital Annals of African Medicine , vol 8, no.3; 2009:
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3.Atarkchi et al Epidemiology ,who is likely to get tetanusBMJ, 1997;1:179
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