WASHINGTON (FRONTLINE MEDICAL NEWS)Older age was a significant predictor of a poor outcome associated with neuroleptic malignant syndrome in a retrospective review of more than 1,700 inpatient cases in the United States over a recent 12-year period.

Other factors that were significant positive predictors of a poor outcome were acute kidney injury, respiratory failure, and seizures, Dr. Sumul Modi said at the annual meeting of the American Academy of Neurology. The study also showed that inpatient mortality due to neuroleptic malignant syndrome (NMS) has significantly dropped since it was first described in 1960.Because NMS is rare, it is difficult to study a large sample of patients, and large real-world studies of NMS are lacking, especially in the last few decades, he said, noting that most of the literature on NMS is from the 20th century.

The aim of this study was to identify predictors of poor outcome associated with NMS, using the National Inpatient Sample , a large, publicly available, all-payer, inpatient health care database that covers about 20% of all admissions to nonfederal hospitals in the United States. ICD-9 diagnostic and procedure were used to identify major complications and procedures. Univariate and multivariate logistic regression analyses were used to identify predictors.

From 2000 through 2011, Dr. Modi, a neurology resident at Henry Ford Hospital, Detroit, and his coauthor identified 1,725 cases in the database with a primary diagnosis of NMS in patients aged 16 and older, making this the largest study of NMS to date. (Cases with a secondary diagnosis that can affect the diagnosis of NMS, including serotonin syndrome and substance abuse, alcohol, or drug withdrawal, were excluded.)

Of these patients, 183 – almost 11% – had a poor outcome, defined as in-hospital death or having undergone a feeding tube placement. Of the total, 99 patients – almost 6% – died while hospitalized.

The most common complication associated with NMS was rhabdomyolysis, in 24%, which was not directly associated with a poor outcome. But other complications – seizures (12.9% of the total), acute kidney injury (15.7%), respiratory failure (11.4%), and cardiac dysrhythmia (8.8%) – were also significantly associated with poor outcome, Dr. Modi said.

Medical complications significantly associated with a poor outcome included pneumonia (reported in 8.5% of the patients with NMS), urinary tract infection (18%), sepsis (6.3%), and acute liver failure (1.3%).

A multivariate analysis, with adjusted odds ratios, determined that the following were predictors of poor outcome: age (OR, 1.5), acute kidney injury (OR, 2.1), acute respiratory failure (OR, 10.7), and seizures (OR, 1.7).

Every calendar year increase was a “small but significant” negative predictor of poor outcome (OR, 0.9). During the period studied, the highest mortality rate – about 9% – was in 2002, dropping to about 2.5% in 2009 and increasing to about 5% in 2010 and 2011. The marked drop in mortality since NMS was first described in 1960 could be due to improved intensive care, but could also be related to the various treatment approaches used, such as dantrolene and dopamine agonists, Dr. Modi said.

Increasing use of atypical antipsychotics may also play a role, but the investigators were not able to determine if patients had been treated with an atypical or typical antipsychotic and what treatments were used to manage NMS, which are limitations of the study, he said. They were also not able to determine if the time to diagnosis played a role in the outcome or whether patients were treated in a tertiary medical center.

Dr. Modi and his coauthor had no disclosures.