Sedation and analgesia in the intensive care unit: evaluating the role of dexmedetomidine.

PURPOSE: A review highlighting the application of sedatives and analgesics in the intensive care unit (ICU) setting, with a focus on the use of dexmedetomidine, is presented. SUMMARY: Relevant and applicable clinical trials that resulted from a search of the literature from 1966 to July 2006 using key search terms such as dexmedetomidine, intensive care unit, sedation, delirium, and analgesia were evaluated. Many agents have been evaluated in the search of the optimal regimen for sedation and analgesia in the ICU, including opioids, benzodiazepines, propofol, and antipsychotic agents. Dexmedetomidine has demonstrated efficacy as a sedative analgesic on the basis of its ability to lower opioid, benzodiazepine, and propofol requirements in clinical trials. The role of dexmedetomidine in ICU clinical practice is limited because of a lack of mortality and other morbidity endpoints, such as ICU length of stay, hospital length of stay, time to extubation, long-term complications after discharge from the ICU, and delirium. The most commonly reported adverse effects of dexmedetomidine are secondary to its effects as an alpha(2)-receptor agonist and are cardiac in nature. A detailed cost analysis may be warranted to justify the relatively high acquisition cost of dexmedetomidine. CONCLUSION: Dexmedetomidine may be an effective agent for ICU sedation and analgesia. However, the lack of clinically relevant endpoints in trials, the concern about adverse cardiovascular effects, and the relatively high acquisition cost of this drug limit its use to a select number of patients who may benefit from its distinguished mechanism of action.

Azacitidine-induced interstitial and alveolar fibrosis in a patient with myelodysplastic syndrome.

A 71-year-old Caucasian man diagnosed with myelodysplastic syndrome developed interstitial and alveolar fibrosis after receiving a 7-day course of azacitidine therapy. The patient's pulmonary function began to deteriorate immediately after the administration of his chemotherapy regimen. Other potential causes of pulmonary toxicity were ruled out such as viral, fungal, and bacterial pathogens, as well as other concomitant drugs. To our knowledge, this is the first case report documenting biopsy-proven interstitial and alveolar fibrosis associated with azacitidine. The frequency of this adverse drug reaction is unknown but may become more evident with increasing exposure of the population to azacitidine.

Interaction between nesiritide and a heparin-coated pulmonary artery line during an infusion for decompensated heart failure.

STUDY OBJECTIVE: Because it is known that intravenous nesiritide is not compatible with unfractionated heparin, we sought to determine the effect that heparin coating on a pulmonary artery catheter may have on the efficacy of a nesiritide infusion. METHODS: The efficacy of a nesiritide infusion given through a heparin-coated pulmonary artery line was compared with that of a nesiritide infusion administered in the same patient through a heparin-free peripheral line. RESULTS: The rate of infusion was titrated to maintain consistent hemodynamic parameters. When nesiritide was administered through a heparin-coated line, the infusion rate escalated from 0.01 microg/kg/minute to 0.07 microg/kg/minute. After the route of administration was switched to a heparin-free line, the same hemodynamic parameters were maintained. The heparin-free line made it possible to reduce the infusion rate by 57.1% over the next 24 hours to 0.03 microg/kg/minute. CONCLUSION: The interaction of nesiritide with heparin-coated pulmonary artery lines has the potential to be clinically significant. Clinicians should be educated about this potential interaction. Nesiritide should be infused only through heparin-free lines.

Calcium channel blockers as the treatment of choice for hypertension in renal transplant recipients: fact or fiction.

Posttransplantation hypertension has been identified as an independent risk factor for chronic allograft dysfunction and loss. Based on available morbidity and mortality data, posttransplantation hypertension must be identified and managed appropriately. During the past decade, calcium channel blockers have been recommended by some as the antihypertensive agents of choice in this population, because it was theorized that their vasodilatory effects would counteract the vasoconstrictive effects of the calcineurin inhibitors. With increasing data becoming available, reexamining the use of traditional antihypertensive agents, including diuretics and beta-blockers, or the newer agents, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers, may be beneficial. Transplant clinicians must choose antihypertensive agents that will provide their patients with maximum benefit, from both a renal and a cardiovascular perspective. Beta-blockers, diuretics, and ACE inhibitors have all demonstrated significant benefit on morbidity and mortality in patients with cardiovascular disease. Calcium channel blockers have been shown to possess the ability to counteract cyclosporine-induced nephrotoxicity. When compared with beta-blockers, diuretics, and ACE inhibitors, however, the relative risk of cardiovascular events is increased with calcium channel blockers. With the long-term benefits of calcium channel blockers on the kidney unknown and a negative cardiovascular profile, these agents are best reserved as adjunctive therapy to beta-blockers, diuretics, and ACE inhibitors.

Efficacy and safety of low-dose valganciclovir for prevention of cytomegalovirus disease in renal transplant recipients: a single-center, retrospective analysis.

STUDY OBJECTIVE: To evaluate the safety and efficacy of valganciclovir 450 mg/day for 6 months for cytomegalovirus (CMV) prophylaxis in renal transplant recipients. DESIGN: Single-center, retrospective analysis. SETTING: Urban, academic medical center. PATIENTS: Fifty-eight patients who received de novo renal transplants from August 1, 2001-November 21, 2002. INTERVENTION: Valganciclovir 450 mg/day was administered to all renal transplant recipients at risk for CMV disease. Therapy was begun postoperatively and was dose adjusted to renal function. MEASUREMENTS AND MAIN RESULTS: Data collected from renal transplant recipients were demographics, immunosuppressive and antiviral drug therapy, and occurrence of CMV disease, acute rejection, allograft loss, and hematologic adverse events. Donor (D)/recipient (R) CMV serostatus was 37.9% D+/R+, 29.3% D-/R+, 17.3% D+/R-, and 15.5% D-/R-. Antithymocyte globulin (ATG) was administered to 62.1% of patients. Most of the transplant recipients received triple immunosuppression as maintenance therapy. Median follow-up was 20 months. The frequency of CMV disease was 1.7% within 6 months after transplantation and 5.2% at any point after transplantation. All patients who developed CMV disease were D+/R- and had received ATG. Leukopenia and thrombocytopenia associated with valganciclovir were seen in 28% and 24% of patients, respectively. One patient developed acute cellular rejection. No graft losses or deaths occurred. Early discontinuation of valganciclovir occurred in 20% of patients secondary to severe, persistent leukopenia, thrombocytopenia, and/or diarrhea. None of these patients developed CMV disease. CONCLUSION: A high rate of CMV disease was noted among the D+/R- population. Administration of ATG as an induction agent also increased the frequency of CMV disease. Despite the low dosage of valganciclovir, hematologic adverse events were common. However, valganciclovir, administered at 450 mg/day for 6 months, was effective and relatively safe for prophylaxis of CMV disease in renal transplant recipients.

Everolimus: a proliferation signal inhibitor with clinical applications in organ transplantation, oncology, and cardiology.

Everolimus, a proliferation signal inhibitor in the mammalian target of rapamycin (mTOR) drug class, has many clinical applications, including in organ transplantation, oncology, and cardiology. It currently has United States Food and Drug Administration (FDA) approval for prophylaxis against rejection in de novo renal transplant recipients, treatment of renal cell carcinoma, and use as a drug-eluting stent. To review the pharmacology, pharmacokinetics, efficacy, and safety of everolimus, we performed a search of the MEDLINE database (January 1997-April 2010) for all English-language articles of in vitro and in vivo studies that evaluated everolimus, as well as abstracts from recent scientific meetings and the manufacturer. In transplantation, everolimus demonstrates immunosuppressive properties and has been used to prevent acute rejection in cardiac, liver, lung, and renal transplant recipients. It appears that this agent may be potent enough to allow for the minimization or removal of calcineurin inhibitors in the long-term management of renal transplant recipients. In oncology, everolimus has been proven effective for the management of treatment-resistant renal cell carcinoma. In cardiology, everolimus is available as a drug-coated stent and is used in percutaneous coronary interventions for prevention of restenosis. In transplant recipients and patients with renal cell carcinoma, everolimus appears to have an extensive adverse-event profile. The pharmacologic properties of everolimus differentiate this agent from other drugs used in these clinical areas, and its pharmacokinetic properties differentiate it from sirolimus.

Evaluation of dexmedetomidine versus propofol-based sedation therapy in mechanically ventilated cardiac surgery patients at a tertiary academic medical center.

Management of pain and sedation therapy is a vital component of optimizing patient outcomes; however, the ideal pharmacotherapy regimen has not been identified in the postoperative cardiac surgery population. We sought to evaluate efficacy and safety outcomes between postoperative mechanically ventilated cardiac surgery patients receiving dexmedetomidine versus propofol therapy upon arrival to the intensive care unit (ICU). We conducted a single center, descriptive study of clinical practice at a 20-bed cardiac surgery ICU in a tertiary academic medical center. Adult mechanically ventilated postcardiac surgery patients who received either dexmedetomidine or propofol for sedation therapy upon admission to the ICU between October 20, 2006 and December 15, 2006 were evaluated. A pharmacy database was used to identify patients receiving dexmedetomidine or propofol therapy for perioperative sedation during cardiac surgery. Patients were matched according to surgical procedure type. Fifty-six patients who received either dexmedetomidine (n = 28) or propofol (n = 28) were included in the analysis. No differences in the ICU length of stay (58.67 ± 32.61 vs. 61 ± 33.1 hours; P = 0.79) and duration of mechanical ventilation (16.21 ± 6.05 vs. 13.97 ± 4.62 hours; P = 0.13) were seen between the propofol and dexmedetomidine groups, respectively. Hypotension (17 [61%] vs. 9 [32%]; P = 0.04), morphine use (11 [39.3%] vs. 1 [3.6%]; P = 0.002), and nonsteroidal anti-inflammatory use (7 [25%] vs. 1 [3.6%]; P = 0.05) occurred more during dexmedetomidine therapy versus propofol. Dexmedetomidine therapy resulted in a higher incidence of hypotension and analgesic consumption compared with propofol-based sedation therapy. Further evaluation is needed to assess differences in clinical outcomes of propofol and dexmedetomidine-based therapy in mechanically ventilated cardiac surgery patients.

Adjuvant ketamine analgesia for the management of cancer pain.

OBJECTIVE: To review the clinical literature evaluating the utilization of intravenous ketamine for the management of cancer-related pain, to summarize the data that suggest ketamine is an appropriate adjuvant method of providing analgesia and to report a case of successful pain management using ketamine in a patient with recurrent testicular cancer at our institution. DATA SOURCES: Primary literature was identified through a MEDLINE search (1966-March 2002), and additional information was obtained through secondary and tertiary sources. DATA SYNTHESIS: The available data suggest that supplementation of morphine with ketamine improves analgesia in patients with cancer, and also provides insight to the controversy regarding the efficacy and adverse effects of various ketamine doses. At subanesthetic doses, ketamine may be beneficial at reducing opioid requirements and related adverse effects. CASE SUMMARY: A 34-year-old white man with recurrent testicular cancer was admitted with radiating neuropathic pain of the legs and lower back. The patient was suspected to also be experiencing opioid adverse effects; therefore, alternative analgesic options were warranted. Ketamine was successful in reducing patient-reported pain and was also well tolerated. CONCLUSIONS: Ketamine is an adjuvant analgesic for the treatment of cancer-related pain when other agents either fail or are intolerable. Accordingly, there are several factors that may prevent adequate pain control with opioid use; therefore, alternative analgesic options should be considered. Promise exists for ketamine as a contemporary analgesic in the appropriate patient.