Description of Pharmacogenomic Testing Among Patients Admitted to the Intensive Care Unit After Cardiovascular Surgery.

BACKGROUND: Pharmacogenomic (PGx) testing has the potential to provide information on specific drug-metabolizing enzymes that may lead to an absence, reduction, or increase in medication effect in patients. There is a paucity of prospective studies examining PGx testing in the intensive care unit (ICU) setting. RESEARCH AIMS: To (1) obtain a PGx panel in a sample of cardiovascular (CV) surgical patients with a planned ICU stay and identify phenotypes, and (2) identify PGx variants that may inform treatment regimens and may warrant prescribing adjustments. DESIGN AND METHODS: Descriptive, single cohort cross-sectional design. Adult (≥18 years) CV patients with an anticipated postoperative ICU stay were enrolled from a large Midwestern tertiary academic medical center. Eligible patients provided informed consent at the time of their CV clinic appointment; PGx testing was then ordered. Pharmacogenomic testing consisted of the Focused Pharmacogenomics panel which included 10 genes and 55 medications. RESULTS: Of the 272 patients screened, 100 (68% male) patients completed PGx testing (mean age 66.2 ± 9.6 years, mean Acute Physiology, Age and Chronic Health Evaluation III score 76.1 ± standard deviation). Pharmacogenomic results were available in the medical record within a median of 52.4 hours (interquartile range: 33.4-80.3). Pharmacogenomic testing results identified 5 CYP2C19 poor metabolizers, 26 CYP2C19 rapid metabolizers, 5 CYP2C19 ultrarapid metabolizers, 6 CYP2D6 poor metabolizers, 5 CYP2D6 poor to intermediate metabolizers, and 2 CYP2D6 rapid metabolizers identified. Overall, 98% of patients had actionable or potentially actionable PGx results, including 82% for warfarin, 65% for propafenone, 65% for tramadol, 46% for oxycodone, 45% for metoprolol, 33% for clopidogrel, 32% for proton pump inhibitors, 25% for statins, and 12% for haloperidol. CONCLUSIONS: A significant portion of patients had identified genetic variants that may warrant changes in medication management during and after CV-ICU stay. It remains to be seen if PGx testing leads to improvements in ICU patient outcomes.

Role of tacrolimus in return of hand function after brachial plexus injury in a lung transplantation patient.

We report a patient who has been on tacrolimus for bilateral lung transplantation and presented with a brachial plexus injury (BPI), with unusual improvement of lower trunk innervated hand function. The lower trunk injury with resultant left hand paralysis had developed after his sternotomy 18 months ago. He has been treated with tacrolimus as part of his immunosuppression protocol since the surgery, without severe side effects. Physical examination at 18 months demonstrated unusual excellent grip pattern and full opposition of his thumb with slight claw deformity of his ulnar two digits. While the neurotoxic effects of tacrolimus are more emphasised, the neuroregenerative properties have been recently explored. The recovery in this patient is unique and unusual after BPI and is most likely as a result of the low dose tacrolimus treatment.

Time to achieving therapeutic international normalized ratio increases hospital length of stay after heart valve replacement surgery.

BACKGROUND: Achieving a therapeutic international normalized ratio (INR) before hospital discharge is an important inpatient goal for patients undergoing mechanical cardiac valve replacement (MCVR). The use of clinical algorithms has reduced the time to achieve therapeutic INR (TTI) with warfarin therapy. Whether TTI prolongs length of stay (LOS) is unknown. METHODS: Patients who underwent MCVR over a consecutive 42-month period were included. Clinical data were obtained from the Society of Thoracic Surgeons Adult Cardiac Surgery database and electronic medical records. Therapeutic INR was defined as per standard guidelines. Warfarin dose was prescribed using an inpatient pharmacy-managed algorithm and computer-based dosing tool. International normalized ratio trajectory, procedural needs, and drug interactions were included in warfarin dose determination. RESULTS: There were 708 patients who underwent MCVR, of which 159 were excluded for reasons that would preclude or interrupt warfarin use. Among the remainder of 549 patients, the average LOS was 6.4days and mean TTI was 3.5days. Landmark analysis showed that subjects in hospital on day 4 (n=542) who achieved therapeutic INR were more likely to be discharged by day 6 compared with those who did not achieve therapeutic INR (75% vs 59%, P<.001). Multivariable proportional hazards regression with TTI as a time-dependent effect showed a strong association with discharge (P=.0096, hazard ratio1.3) after adjustment for other significant clinical covariates. CONCLUSIONS: Time to achieve therapeutic INR is an independent predictor of LOS in patients requiring anticoagulation with warfarin after MCVR surgery. Alternative dosing and anticoagulation strategies will need to be adopted to reduce LOS in these patients.