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To the Editor: Children who survive meningococcal septic shock syndrome (MSSS) may have long-term lung damage secondary to mechanical ventilation or to the disease itself. We studied the long-term pulmonary sequelae of MSSS and their relationship with several clinical variables during the acute phase of the disease.

Methods
We measured lung function parameters (forced expiratory volume in 1 second, forced vital capacity, total lung capacity, residual volume, and diffusing capacity of carbon monoxide) and transcutaneous arterial oxygen saturation (SaO₂) during maximal exercise in 18 children an average of 3.4 years (range, 2.2-4.9 years) after receiving mechanical ventilation for MSSS. Median age at the acute phase of disease was 4.7 years (range, 1.6-15.4 years).

Results
At follow-up, all children had normal lung function parameters and SaO₂ values at rest. During maximal exercise, the median decrease in SaO₂ was 2.5% (range, 0%-20%). In 6 children (desaturation group), SaO₂ dropped below 95% (median decrease from resting value, 12.5%; range 5%-20%).

None of the ventilatory parameters during the first 24 hours of the acute illness were associated with exercise-induced desaturation using repeated measures analysis of variance. However, children in the desaturation group had consistently lower peripheral temperatures during the first 24 hours of the acute illness, with a mean 3.3°C (95% confidence interval [CI], 1.4°C-5.2°C) lower peripheral temperature, which remained constant over time (ie, there was no group by time interaction). There were no statistical differences in central temperature.

We also compared groups on results of prior blood gas analyses (pH, partial pressure of carbon dioxide, partial pressure of oxygen, base excess, and bicarbonate level), hematological parameters (hemoglobin, leukocyte count, and platelet count) and the overall Pediatric Risk of Mortality (PRISM) score¹ on day 1 and day 2 of the original hospitalization. All hematological variables were obtained prior to any transfusion. We also compared the groups on a number of metabolic variables (fluid balance and blood urea nitrogen, creatinine, sodium, potassium, glucose, calcium, albumin, C-reactive protein, and lactic acid levels) on day 2 only, after the patients had been stabilized. We used the most abnormal value for each variable on each day and compared the groups by using 2-sided Mann-Whitney U tests.

The desaturation group had higher PRISM scores (16.5 vs 10; P = .03) and lower platelet counts (49.5 x 10⁹ vs 143.5 x 10⁹; P = .008) on day 1, although differences in these variables were not significant on day 2. The desaturation group had higher C-reactive protein levels (265 mg/L vs 148 mg/L; P = .04) and fluid balance (97.0 mL/kg vs 8.1 mL/kg; P = .01) on day 2.

Comment
We found a high incidence (33%) of long-term exercise-induced deoxygenation in children who survived MSSS. None of the initial ventilatory parameters were related to this outcome, although other studies have shown that mechanical ventilation can be associated with long-term lung dysfunction.² Perhaps this can be explained by the current use of lung-protective ventilator strategies.³

Children in the desaturation group had significantly higher PRISM scores during the initial phase of their illness, suggesting that exercise-induced desaturation is related to the initial severity of meningococcal disease.⁴ Although other clinical parameters in the acute phase were significantly related to outcome, these results should be interpreted with caution in light of the large number of statistical comparisons and small sample size.

Circulatory failure and disseminated intravascular coagulation are the predominant clinical features of MSSS and lead to formation of microthrombi in all organs, which eventually may lead to necrosis of the skin extremities.⁵ Furthermore, several reports have described skeletal lesions consistent with osteonecrosis,⁶ which may manifest as growth abnormality months or years after the acute disease. It is possible that similar vasculitis and microthrombi in peripheral lung arterioles and venules during the acute phase and subsequent pulmonary vascular remodeling may result in long-term desaturation during maximal exercise.

Frans B. Plötz, MD,PhD; Hans van Vught, MD,PhD
Department of Pediatric Intensive Care

Cuno S. P. M. Uiterwaal, MD,PhD
Julius Center for Patient-Oriented Research

Maaike Riedijk; Cornelis K. van der Ent, MD,PhD
Department of Pediatric Pulmonology
University Medical Center
Utrecht, the Netherlands

1. Gemke RJ, Bonsel GJ, McDonell J, van Vught AJ. Patient characteristics and resource utilisation in peadiatric intensive care. Arch Dis Child. 1994;71:291-296. FREE FULL TEXT 2. Davidson TA, Caldwell ES, Curtis JR, Hudson LD, Steinberg KP. Reduced quality of life in survivors of acute respiratory distress syndrome compared with critically ill control patients. JAMA. 1999;281:354-360. FREE FULL TEXT 3. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Eng J Med. 2000;342:1301-1308. FREE FULL TEXT 4. van Brakel MJ, van Vught AJ, Gemke RJ. Pediatric risk of mortality (PRISM) score in meningococcal disease. Eur J Pediatr. 2000;159:232-236. FULL TEXT | PUBMED 5. de Kleijn ED, Hazelzet JA, Komelisse RF, et al. Pathophysiology of meningococcal sepsis in children. Eur J Pediatr. 1998;157:869-880. FULL TEXT | ISI | PUBMED 6. Campbell WN, Joshi M, Sileo D. Osteonecrosis following meningococcemia and disseminated intravascular coagulation in an adult: case report and review. Clin Infect Dis. 1997;24:452-455. ISI | PUBMED

Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.

JAMA. 2001;285:293-294.

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