There have been descriptive studies from India on diphtheria(5,6) but none have focused on predictors of outcome and the impact of intensive care in these patients. The objective of this study was to examine the outcome and predictors of mortality of diphtheria in children receiving intensive care. This would help in early identification of the severity of illness and prioritization of intensive care especially in developing countries with limited resources.

Forty eight consecutive patients with a clinical diagnosis of diphtheria(7), admitted to PICU of a tertiary care teaching hospital, between December 1994 to 2002 (9 years) were analyzed retrospectively with respect to demographic details, clinical features, immunization status, complications and mortality. Several variables were compared among the survivors and non-survivors to define the predictors of outcome. Outcome was defined as either recovered or died.

Children were considered adequately immunized if they had received three or more doses of diphtheria toxoid containing vaccine by age 2 years (primary series)(8).

All children with a clinical suspicion of diphtheria were started on parenteral crystalline penicillin in the dose of 50,000 U-1,00,000 U in 4 divided doses. Antidiphtheritic serum (ADS) was given in a single dose as recommended(9) depending on the site and extent of disease. Throat swab for Albert’s stain and culture were sent in all, at the time of admission. Patients with anticipated/ established features of any complications like airway obstruction, myocarditis, renal failure and thrombocytopenia were shifted to PICU for monitoring and management. After December 1997, all patients with diphtheria were started routinely on L-carnitine 50-100 mg/kg/day in 3 divided doses. Close contacts of the patient were administered erythromycin prophylaxis of 50 g/kg/day day in 4 divided doses for 7 days.

Data are presented as mean (SD) and median (range). Between groups comparison was done using Chi-square test for categorical data and Students’ t-test and Mann Whitney U test for parametric and non-parametric data respectively. Survivors and non-survivors were compared using a univariate analysis to identify predictors having a significant association with mortality. Odd’s ratio with 95% CI was computed for the significant variables. All variables found to be significant on univariate analysis (P <0.05), were subjected to multiple logistic regression analysis, to determine the significant predictors of mortality.

The age and sex distribution, clinical features, immunization status and complications of the study population are shown in Table I.

Table I

Clinical Characteristics of 48 Patients with Diphtheria.

Age (yrs) mean ± SD (range)

5.15 ± 2.08 (1-9.5) 

Sex ratio (boys : girls)

2.2 : 1

  Faucial 

33 (68.8) 

  Pharyngolaryngeal 

12 (25)

  Laryngeal

 1 (2.1)

  Faucial + nasal

2 (4.2)

  Unimmunised 

27 (56.3) 

  Partially immunised 

11 (22.9)

  Adequately immunised 

4 (8.3)

  Unknown

6 (12.5)

Albert stain positive, n(%)

17 (35.4)

Culture positive, n(%)

10 (20.8)

  Fever

48 (100)

  Bull Neck

32 (66.7)

  Stridor

30 (62.5)

  Hoarse voice

19 (39.5)

  Difficulty in swallowing

16 (33) 

  Throat pain

11 (23)

  Bleeding

4 (8.4)

  Hypotension at admission

7 (14.6)

  Airway compromise

34 (70.8%)

  Myocarditis

32 (66.7%)

  Renal failure

17 (35.4%)

  Thrombocytopenia

15 (31.3%)

Of 34 patients with airway compromise, 24 (70.6%) had associated myocarditis and 10 (29.4%) had isolated airway problems. Tracheostomy was performed in all patients with airway compromise, without any procedural complication. Five patients were intubated for airway relief at the first instance; two of them died during intubation; one of whom had associated myocarditis. The other three needed tracheostomy later on.

Two deaths occurred among 10 patients with isolated airway obstruction one related to bleed in the airway and the other an intubation related complication.

The mean interval between onset of respiratory symptoms and myocarditis was 6.5 ± 2.4 days (range 1-11 days). Twenty (62.5%) of these children presented with conduction abnormalities and cardiogenic shock; other presentations included isolated cardiogenic shock (n = 6; 18.8%), arrhythmia (n = 5; 15.6%) and CCF (n = 1; 3.1%). Bundle branch block (BBB) was observed in 15 patients; 9 of them progressed to complete heart block. Ten patients had tachyarrhythmias (6 ventricular tachycardia, and 2 each of supra-ventricular and junctional tachycardia) Temporary pacing was done in 7 patients with complete heart block but none of them survived. Univariate analysis revealed that inadequate immunity, longer duration of bull neck and delayed administration of ADS were associated with development of myocarditis (Table II). However, on multiple logistic regression analysis, none of the variables were significant predictors of myocarditis.

Of the 32 patients with myocarditis 25(78.1%) died (Odd’s ratio 25, 95% CI 3.4 - 210.3, P = 0.0001); eighteen due to conduction abnormality and cardiogenic shock, 3 secondary to isolated shock and 2 due to arrhythmia. Presence of cardiogenic shock was associated with the highest mortality (OR 33.3; 95% CI 5.0 - 287.6; P = 0.0001).

Of the 17 patients with renal failure; 3 patients were dialysed. Fifteen children with renal failure died; all of them had myocarditis and cardiogenic shock (OR 11.9, 95% CI 2-91.5, P = 0.0001).

Of the 15 children with thrombocytopenia (platelet count <150,000/cu mm), 9 manifested with skin and mucosal bleeds and 10 died (OR 1.9,95% CI 0.45 - 8.2, P = 0.32); all but one had associated myocarditis.

Out of 48 patients, 21 survived and 27 died (56.3%). The immediate cause of death was myocarditis 23 (85%), airway compromise 3 (11.1%) and 1 septic shock due to nosocomial sepsis. The immunization status had a significant association with both clinical severity and outcome. One out of 4 with adequate immunization developed myocarditis as against 9 out of 11 with partial immunization (P = 0.039). There were no deaths in the immunized group in contrast to 7 and 15 deaths in the partially and completely unimmunised group respectively (P = 0.029).

On comparing survivors with non-survivors, we found that the latter were inadequately immunized, had presented more often with hypotension at admission itself and had increased incidence of complications like myocarditis, airway compromise and renal failure (Table III). On multiple regression analysis development of myocarditis was the only independent predictor of death. (Adjusted Odds’ ratio 0.061, 95% CI 0.009 - 0.397; P = 0.003).

Upper airway obstruction was the commonest complication seen in nearly three fourths of our patients, much higher than the 4-15% reported previously(10). Since only one fourth of our patients had laryngeal involvement, the other possible factors operating for airway obstruction could have been extensive pharyngotonsillar disease, florid soft tissue edema and necrosis or bleeding into the airways. This highlights the fact that signs of upper airway obstruction may occur in children with or without a laryngeal membrane and should be anticipated and aggressively treated.

Intubation in our experience was not a very successful airway relief procedure, as three of our intubated patients required subsequent tracheostomy and two others succumbed to procedure related problems. This was possibly related to the friable upper airways making the procedure difficult. Also it carries with it a high risk of dislodgement of the pseudomembrane. We found that tracheostomy was better, similar to previous observations(11). Perhaps it provided better conduit for tracheal toileting and was easier to maintain as compared to the endotracheal tube. Thus, prognosis with airway complications is good with timely interventions; with tracheostomy providing a safe and effective form of airway relief.

The incidence of myocarditis (66.6%) in our patients was also much higher than previously reported(6,12). Also, contrary to its typical description as end of second week complication, our patients had earlier onset time of less than a week from the onset of the upper respiratory disease(10,13).

We found conduction abnormalities leading to cardiogenic shock was the commonest manifestation, with bradyarrythmias in the form of BBB being more frequent than tachyarrhythmias. Both these findings were in concordance with previous studies(13,14).

Of the treatment options available, neither carnitine(15) nor pacing(14) has proven to be of any benefit.

The two factors studied to have some role in preventing myocarditis are adequate immunization and early administration of ADS (3,11,16). Case fatality rates in those who received antitoxin after a week were higher than in those who received ADS at the onset of respiratory illness(16). In our study too, myocarditis was more often seen in patients with inadequate immunization, and delayed treatment with ADS. These findings imply that myocarditis in unimmunised and partially immunized children with diphtheria can be fulminant. A high index of suspicion should be maintained in those with severe bull neck, and antitoxin given immediately, pending diagnostic confirmation. Availability of antitoxin must be ensured at all times.