Morphological abnormalities in baseline ECGs in healthy normal volunteers participating in phase I studies.

Background & objectives: Morphological abnormalities in 12-lead electrocardiograms (ECGs) are seen in subgroups of healthy individuals like athletes and air-force personnel. As these populations may not truly represent healthy individuals, we assessed morphological abnormalities in ECG in healthy volunteers participating in phase I studies, who are screened to exclude associated conditions. Methods: ECGs from 62 phase I studies analyzed in a central ECG laboratory were pooled. A single drug-free baseline ECG from each subject was reviewed by experienced cardiologists. ECG intervals were measured on five consecutive beats and morphological abnormalities identified using standard guidelines. Results: Morphological abnormalities were detected in 25.5 per cent of 3978 healthy volunteers (2495 males, 1483 females; aged 18-76 yr); the presence was higher in males (29.3% vs. 19.2% in females; P<0.001). Rhythm abnormalities were the commonest (11.5%) followed by conduction abnormalities (5.9%), axis deviation (4%), ST-T wave changes (3.1%) and chamber enlargement (1.4%). Incomplete right bundle branch block (RBBB), short PR interval and right ventricular hypertrophy were common in young subjects (<20 yr) while atrial fibrillation, first degree atrioventricular block, complete RBBB and left anterior fascicular block were more prevalent in elderly subjects (>65 yr). Prolonged PR interval, RBBB and intraventricular conduction defects were more common in males while sinus tachycardia, short PR interval and non-specific T wave changes were more frequent in females. Interpretation & Conclusions: Morphological abnormalities in ECG are commonly seen in healthy volunteers participating in phase I studies; and vary with age and gender. Further studies are required to determine whether these abnormalities persist or if some of these disappear on follow up.

Tropical infections in the ICU.

Certain arthropod-borne infections are common in tropical regions because of favorable climatic conditions. Water-borne infections like leptospirosis are common due to contamination of water especially during the monsoon floods. Infections like malaria, leptospirosis, dengue fever and typhus sometimes cause life threatening organ dysfunction and have several overlapping features. Most patients present with classicial clinical syndromes: fever and thrombocytopenia are common in dengue, malaria and leptospirosis; coagulopathy is frequent in leptospirosis and viral hepatitis. Hepatorenal syndrome is seen in leptospirosis, falciparum malaria and scrub typhus. The pulmonary renal syndrome is caused by falciparium malaria, leptospirosis, Hantavirus infection and scrub typhus. Fever with altered mental status is produced by bacterial meningitis, Japanese B encephalitis, cerebral malarial, typhoid encephalopathy and fulminant hepatic failure due to viral hepatitis. Subtle differences in features of the organ failure exist among these infections. The diagnosis in some of these diseases is made by demonstration of antibodies in serum, and these may be negative in the first week of the illness. Hence empiric therapy for more than one disorder may be justified in a small proportion of cases. In addition to specific anti-infective therapy, management of organ dysfunction includes use of mechanical ventilation, vasopressor drugs, continuous renal replacement therapy and blood products. Timely transfer of these patients to well-equipped ICUs with experience in managing these cases can considerably decrease mortality and morbidity.

New onset fever in the intensive care unit.

Fever is defined as a core body temperature of >38.3 degrees C or 101 degrees F. About 50% of fevers in the ICU are due to infectious causes. Absence of fever in patients with infection heralds a poor prognosis. Temperatures between 102 degrees F-106 degrees F are more likely to be due to infection. The common infectious causes of fever are pneumonia, urosepsis, line infections and intraabdominal infections. Temperatures <102 degrees F or >106 degrees F are usually due to non-infectious causes like deep venous thrombosis, infusion reactions, aspiration, drug fever and the neuroleptic malignant syndrome. Fever should be distinguished from hyperthermia as antipyretics are ineffective in the latter. Inappropriate use of antibiotics selects resistant bacterial strains, but delay in treating infection could increase mortality. A structured approach is therefore required in order to correctly diagnose and treat fever in critically ill patients.

Control of rate versus rhythm in rheumatic atrial fibrillation: a randomized study.

BACKGROUND: Patients with rheumatic heart disease and atrial fibrillation incur significant morbidity and mortality. It is not known which approach, rate control or maintenance of sinus rhythm might be most appropriate. The present study was undertaken to compare the strategy of ventricular rate control versus maintenance of sinus rhythm in rheumatic atrial fibrillation, and to evaluate the role of amiodarone in this patient population. METHODS AND RESULTS: We prospectively studied 144 patients with chronic rheumatic atrial fibrillation in a double-blind protocol-rhythm control (group I: 48 patients each with amiodarone -group Ia; and placebo -group Ib) and compared the effects with the ventricular rate control (group II) by diltiazem (n=48, open-label). Direct current cardioversion was attempted in group I. The mean age of the study population was 38.6+/-10.3 years, left atrial size was 4.7+/-0.6 cm, atrial fibrillation duration was 6.1+/-5.4 years, and 72.9% patients had undergone valvular interventions. At 1 year, 45 patients with sinus rhythm in group I compared to 48 patients in group II demonstrated significant increase in exercise to sinus rhythm time, had improvement in functional class and quality of life score. There was no difference in hospitalization rates, systemic bleeds or incidence of thromboembolism. Five patients died in group II but none in group I (p=0.02). In group I, 73/87 (83.9%) patients converted, and 45/86 (52.3%) patients maintained sinus rhythm at 1 year. Conversion rates were 38/43 (88.4%) with amiodarone versus 34/44 (77.3%) with placebo (p=0.49): corresponding rate for maintaining sinus rhythm was 29/42 (69.1%) versus 16/44 (36.4%), p=0.008 respectively. CONCLUSIONS: Maintenance of sinus rhythm appeared to be superior to ventricular rate control in patients with rheumatic atrial fibrillation in terms of an effect on mortality and morbidity. Sinus rhythm could be restored in the majority and amiodarone was superior to placebo in this regard.