Does Nicotine Replacement Therapy Increase ICU Mortality?

Key Point

Nicotine replacement therapy may be associated with increased mortality in the ICU.

Despite case reports that suggest the potential effectiveness of using nicotine replacement therapy (NRT) to improve patient outcomes in the ICU, no study has examined whether it is safe, or what risks may be involved. According to a report in the June Critical Care Medicine, NRT may be associated with increased hospital mortality in critically ill patients.

“Our study highlights the need for clinicians to be aware of the potential adverse effects of NRT before initiating treatment in critically ill medical patients,” Amy H. Lee, MD, and Bekele Afessa, MD, pointed out. “In the absence of clinical trials in the ICU, our knowledge about the potential risks and benefits of NRT is based on anecdotal case reports.”

Drs. Lee and Afessa, from the divisions of pulmonary and critical care medicine at the University of Pittsburgh and the Mayo Clinic, respectively, performed a retrospective case-control study in which data from patients’ electronic and paper medical records and the APACHE III were abstracted. Among 6,735 admissions to the ICU of a tertiary academic hospital, NRT was initiated in 115 patients who were active smokers. Data for 25 of these patients were excluded from the analysis: Seven patients were missing key data, six patients did not have research authorization, and 12 patients received their first NRT 24 hours post-ICU admission. The remaining 90 active smokers who received NRT were compared with 90 active smokers in the ICU who did not. There were 40 different diagnoses among all 180 patients; the most common diagnosis, drug overdose, was reported among 53 patients (59%) in the NRT group and 42 patients (47%) in the control group. Illness severity as determined by APACHE III did not show any significant differences between the two groups.

The mean predicted mortality rate was 9.2% for the NRT group, compared with 10.3% for the controls. However, analysis showed that 18 patients in the NRT group died, compared with six patients in the control group, which corresponded to hospital mortality rates of 20% and 7% for NRT patients and controls, respectively. In the NRT group, four patients died of pneumonia, three of sepsis, three of respiratory failure, two of anoxic encephalopathy, two of ARDS, two of cardiomyopathy, one of gastrointestinal bleeding, and one of multiple organ failure. In the control group, two patients died of sepsis, one of respiratory failure, one of multiple organ failure, one of liver failure, and one of pulmonary embolism. ICU-free days during the 28-day period after ICU admission averaged 20.7 in the NRT group, compared with 23.4 in the control group. Furthermore, there was an independent association between NRT and increased mortality after adjustment for illness severity and invasive mechanical ventilation.

POTENTIAL MECHANISM

Drs. Lee and Afessa posited that the hemodynamic effects of nicotine—increased heart rate, blood pressure, and myocardial contractility—could cause adverse events for critically ill patients.

“NRT has less risk than cigarette smoking because it does not lead to increased carbon monoxide and hypercoagulable state,” the investigators pointed out. “However, its effect of increasing myocardial oxygen consumption during times of reduced oxygen delivery may lead to adverse outcome in critically ill patients. Although our study does not address the mechanism, it suggests the potential harm of NRT for critically ill patients.”

Despite these findings suggesting a potentially harmful link between NRT and patients in the ICU, Drs. Lee and Afessa stated, “[W]e do not expect the amount of nicotine absorbed during NRT to be large enough to explain the increased death rate in our study.” The researchers pointed out several limitations to their research that warrant “future studies based on better case-control design before specific recommendations are made about the use of NRT in the critically ill.”

For example, the lack of an intermediate care unit resulted in a significant number of patients with drug overdose who required low-risk monitoring to be admitted to the ICU, although “the association between NRT and increased risk of death was limited to the nondrug overdose group,” the researchers noted. In addition, information regarding the degree and duration of current or lifetime tobacco use was not available for the study, and thus the researchers were unable to match patients based on this data.

Despite the study’s limitations, “[c]linicians prescribing NRT in the critically ill need to weigh the risks and benefits associated with it,” Drs. Lee and Afessa recommended. “The fact that NRT is safe in stable patients should not be extrapolated to critically ill patients, who often suffer from severe hemodynamic compromise and multiple organ failure.”               

—John Merriman

Reference
Lee AH, Afessa B. The association of nicotine replacement therapy with mortality in a medical intensive care unit. Crit Care Med. 2007;35(6):1517-1521.

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