Delayed Onset of Central Diabetes Insipidus With Ketamine Sedation: A Report of 2 Cases.

Ketamine is being prescribed with greater frequency due to an emphasis on multimodal analgesia. With increasing use, uncommon adverse effects associated with ketamine are likely to surface. Limited reports of transient central diabetes insipidus (DI) occurring early after initiation (ie, within 10 hours) of ketamine have been reported. We present 2 cases of delayed onset (32 hours or more after initiation), ketamine-induced, transient central DI in patients cannulated for venovenous extracorporeal membranous oxygenation. No other causes of central DI were determined based upon physical examination or laboratory data, and both patients responded to treatment with desmopressin/vasopressin. The Naranjo adverse drug reaction probability scale noted a probable causation for each case. These cases demonstrate the possibility of a rare but serious complication of ketamine. Improvement after discontinuation of ketamine and administration of desmopressin/vasopressin appear to support a drug-effect association.

Associated Mortality of Liberal Fluid Administration in Sepsis.

Fluid resuscitation, to restore intravascular volume and improve oxygen delivery, is a crucial step in early resuscitation efforts of patients with sepsis or septic shock. The 2016 Surviving Sepsis Campaign guidelines suggest the use of dynamic versus static measures of fluid responsiveness and fluid resuscitation with at least 30 mL/kg of intravenous crystalloid within the first 3 hours followed by fluid administration if hemodynamic factors continue to improve. Despite these recommendations, risks to this practice may exist as multiple studies have demonstrated an association between a positive fluid balance and/or administration of large fluid volume and increase in mortality. These studies are limited by variations in their methodologic design; therefore, cause and effect cannot yet be determined. Future multicenter, randomized, controlled studies that evaluate fluid balance and fluid volume need to be conducted to clarify the role of fluid administration to patients with sepsis to maximize benefits and minimize risk.

Cangrelor Bridge Therapy for Gastroduodenal Biopsy.

Dual antiplatelet therapy (DAPT) is the key for secondary prevention of acute coronary syndromes and percutaneous coronary intervention with stent placement. Premature discontinuation of DAPT can result in an increase in cardiac ischemic events and death. If early interruption of DAPT for urgent procedures or surgery is necessary, then ischemic and bleed risks must be balanced with bridging therapy. To date, no medications have a Food and Drug Administration indication for antiplatelet bridge therapy. We present a case of a woman with a history of gastrointestinal bleeding on DAPT for a drug-eluting stent who received cangrelor as bridge therapy prior to gastroduodenal biopsy.

Emerging role of ivabradine for rate control in atrial fibrillation.

Control of ventricular rate is recommended for patients with paroxysmal, persistent, or permanent atrial fibrillation (AF). Existing rate-control options, including beta-blockers, nondihydropyridine calcium channel blockers, and digoxin, are limited by adverse hemodynamic effects and their ability to attain target heart rate (HR). Ivabradine, a novel HR-controlling agent, decreases HR through deceleration of conduction through If ('funny') channels, and is approved for HR reduction in heart failure patients with ejection fraction less than 35% and elevated HR, despite optimal pharmacological treatment. Because If channels were thought to be expressed solely in sinoatrial (SA) nodal tissue, ivabradine was not investigated in heart failure patients with concomitant AF. Subsequent identification of hyperpolarization-activated cyclic nucleotide-gated cation channel 4 (HCN4), the primary gene responsible for If current expression throughout the myocardium, stimulated interest in the potential role of ivabradine for ventricular rate control in AF. Preclinical studies of ivabradine in animal models with induced AF demonstrated a reduction in HR, with no significant worsening of QT interval or mean arterial pressure. Preliminary human data suggest that ivabradine provides HR reduction without associated hemodynamic complications in patients with AF. Questions remain regarding efficacy, safety, optimal dosing, and length of therapy in these patients. Prospective, randomized studies are needed to determine if ivabradine has a role as a rate-control treatment in patients with AF.

High On-Treatment Platelet Reactivity Associated With Prasugrel.

Objective: To report a case of high on-treatment platelet reactivity (HTPR) with prasugrel maintenance therapy despite adequate initial platelet response to a loading dose. Case Summary: A 51-year-old woman presented to the emergency department complaining of chest pain. She was diagnosed with acute-on-chronic systolic heart failure and non-ST-elevated myocardial infarction (MI). She had a previous MI with bare metal stent placement and was taking aspirin and prasugrel 10 mg daily. Once admitted, a P2Y12 assay revealed HTPR (331 PRU); therefore, prasugrel was reloaded (60 mg). The next day a P2Y12 assay showed adequate platelet reactivity inhibition (118 PRU), so prasugrel 10 mg daily was continued in the hospital and on discharge. Seventeen days after discharge she was readmitted for possible ischemia. On day 3 of admission, a P2Y12 assay revealed HTPR (278 PRU); subsequently, prasugrel was discontinued and ticagrelor started. After 3 doses of ticagrelor, a P2Y12 assay was 97 PRU, so ticagrelor was continued. Five months have passed since discharge. The patient continues to take ticagrelor and has had no further cardiac events. Discussion: HTPR indicates hypo- or nonresponsiveness for antiplatelet agents and may result in serious adverse events. HTPR has rarely been reported with prasugrel or ticagrelor. An objective causality assessment of our case revealed a probable association between HTPR and prasugrel. Conclusion: Patient education and recognition of signs and symptoms associated with prasugrel HTPR may prevent morbidity and mortality from treatment failure. Additional research may determine incidence, risk factors, and optimal management of HTPR with prasugrel.

Angiotensin-converting enzyme inhibitors for intermittent claudication associated with peripheral arterial disease.

OBJECTIVE: To review published literature regarding the effectiveness of angiotensin-converting enzyme (ACE) inhibitors for managing intermittent claudication (IC) associated with peripheral arterial disease (PAD). DATA SOURCES: A search of MEDLINE/PubMed (1966-July 2013) using the MeSH terms intermittent claudication and angiotensin-converting enzyme inhibitors was conducted. Limits included articles written in English with human participants. Additional data were identified through bibliographic reviews. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data sources were evaluated. Clinical trials and meta-analyses were included if they evaluated the efficacy of ACE inhibitors for improving functional capacity of patients with PAD with IC. In all, 9 clinical trials and 1 meta-analysis were identified and included for review. ACE inhibitors evaluated in the studies were captopril, lisinopril, perindopril, quinapril, and ramipril. DATA SYNTHESIS: Current medications approved for treating the symptoms and improving function in PAD with IC have limited efficacy. It has been suggested that ACE inhibitors may be effective in PAD with IC. Though data evaluating ACE inhibitors as a class in this patient population are conflicting, results of the largest and longest trial reported that ramipril increases maximum walking time and pain-free walking time and improves quality of life in patients with PAD with IC. CONCLUSIONS: ACE inhibitors may provide some relief of IC symptoms when used in patients with PAD. The greatest functional benefit has been seen with ramipril; it is unknown whether other agents in the class would show similar results. Well-controlled and designed studies with sufficient power and using diverse patient populations are needed.

Alemtuzumab for cytolytic induction of immunosuppression in heart transplant recipients.

OBJECTIVE: To review available evidence about the safety and efficacy of alemtuzumab for induction of immunosuppression in heart transplant recipients. DATA SOURCES: Searches of MEDLINE, EMBASE, and Cochrane databases were conducted. Key search terms included alemtuzumab, Campath-1H, CD52, lymphocyte, cytolytic, induction, immunosuppression, rejection, and cardiac transplantation. Additional pertinent data were identified through a search of abstracts from major transplant meetings. STUDY SELECTION AND DATA EXTRACTION: All English-language articles and abstracts identified from the data sources were evaluated. All primary data were eligible for inclusion if they evaluated the safety or efficacy of alemtuzumab for induction of immunosuppression in heart transplant patients. One retrospective cohort, 1 case series, 1 case-control series, and 1 open-label trial were identified and included for review. DATA SYNTHESIS: Acute cellular rejection occurs in 40% to 70% of heart transplant recipients within the first 6 months after transplant and is associated with significant morbidity and mortality. Depleting and nondepleting antibodies have displayed positive outcomes in inducing immunosuppression; however, the ideal induction strategy that balances efficacy and toxicity remains elusive. Alemtuzumab, a cytolytic anti-CD52 antibody, has been used to induce immunosuppression in kidney, pancreas, liver, intestine, and lung transplant recipients, and its use in heart transplant has been investigated. Studies of use of alemtuzumab to induce immunosuppression in heart transplant patients have shown low rates of rejection; however, it has not been directly compared with other immunosuppression-inducing agents and safety data are limited. CONCLUSIONS: Although alemtuzumab may be a practical option for inducing immunosuppression, data are insufficient to recommend its routine use in deference to more established agents. Large, randomized clinical trials with extended durations of follow-up must be conducted to characterize its efficacy and safety further.

Colchicine for the primary prevention of the postpericardiotomy syndrome.

OBJECTIVE: To review literature regarding the safety and efficacy of colchicine for the primary prevention of the postpericardiotomy syndrome (PPS). DATA SOURCES: Searches of MEDLINE (1966-April 2011) and Cochrane Database (1993-April 2011) were conducted. Key search terms included postpericardiotomy syndrome, postcardiac injury syndrome, and colchicine. Limits were set for articles written in English with human subjects. Additional data were identified through bibliographic reviews. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data sources were evaluated. All primary data were eligible for inclusion if they evaluated the safety and/or efficacy of colchicine for the primary prevention of PPS. Two prospective trials were identified and included for review. DATA SYNTHESIS: PPS occurs in 10-40% of patients who undergo cardiac surgery and is associated with significant morbidity. Effective medications used for the treatment of PPS include nonsteroidal antiinflammatory drugs or corticosteroids. Unfortunately, effective drug therapy for the primary prevention of PPS does not exist. Colchicine, an antiinflammatory agent with possible immunopathic antifibroblast properties, has shown benefit in the treatment and secondary prevention of pericarditis; thus, its use for primary prevention of PPS has been investigated. Limited data evaluating colchicine for the primary prevention of PPS have been published. However, results of the largest, well-designed trial showed positive efficacy outcomes for colchicine reducing the incidence of PPS with minimal adverse effects. CONCLUSIONS: At this time, there are not sufficient data to recommend colchicine as routine therapy for the primary prevention of PPS in patients undergoing cardiac surgery. Large clinical trials need to be conducted.

Pharmacotherapy for mechanical circulatory support: a comprehensive review.

OBJECTIVE: To provide a comprehensive review of the pharmacotherapy associated with the provision of mechanical circulatory support (MCS) to patients with end-stage heart failure and guidance regarding the selection, assessment, and optimization of drug therapy for this population. DATA SOURCES: The MEDLINE/PubMed, EMBASE, and Cochrane databases were searched from 1960 to July 2010 for articles published in English using the search terms mechanical circulatory support, ventricular assist system, ventricular assist device, left ventricular assist device, right ventricular assist device, biventricular assist device, total artificial heart, pulsatile, positive displacement, axial, centrifugal, hemostasis, bleeding, hemodynamic, blood pressure, thrombosis, antithrombotic therapy, anticoagulant, antiplatelet, right ventricular failure, ventricular arrhythmia, anemia, arteriovenous malformation, stroke, infection, and clinical pharmacist. STUDY SELECTION AND DATA EXTRACTION: All relevant original studies, meta-analyses, systematic reviews, guidelines, and reviews were assessed for inclusion. References from pertinent articles were examined for content not found during the initial search. DATA SYNTHESIS: MCS has advanced significantly since the first left ventricular assist device was implanted in 1966. Further advancements in MCS technology that occurred in the latter decade are changing the overall management of endstage heart failure care and cardiac transplantation. These pumps allow for improved bridge-to-transplant rates, enhanced survival, and quality of life. Pharmacotherapy associated with MCS devices may optimize the performance of the pumps and improve patient outcomes, as well as minimize morbidity related to their adverse effects. This review highlights the knowledge needed to provide appropriate clinical pharmacy services for patients supported by MCS devices. CONCLUSIONS: The HeartMate II clinical investigators called for the involvement of pharmacists in MCS patient assessment and optimization. Pharmacotherapeutic management of patients supported with MCS devices requires individualized care, with pharmacists as part of the team, based on the characteristics of each pump and recipient.

Intrapericardial triamcinolone administration for autoreactive pericarditis.

OBJECTIVE: To review published literature regarding the safety and effectiveness of intrapericardial triamcinolone for the treatment of autoreactive pericarditis. DATA SOURCES: Searches of MEDLINE (1966-June 2010) and Cochrane Database (1993-June 2010) were conducted. Limits included articles published in English reporting on human subjects. Additional data were identified through bibliographic reviews. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data sources were evaluated. Trials, studies, and case reports were eligible for inclusion if they evaluated the safety and/or efficacy of intrapericardial triamcinolone for the management of autoreactive pericarditis. DATA SYNTHESIS: Systemic corticosteroids offer an effective treatment option for autoreactive pericarditis; however, their use is limited by adverse effects and they are an independent risk factor for pericarditis recurrence. One case series and 3 open-label trials evaluating intrapericardial triamcinolone for the management of autoreactive pericarditis are reviewed. Included studies were limited by small sample sizes (N = 2-84), lack of control groups, short durations of follow-up (24 h to 12 mo), use of adjuvant agents, omission of patient demographic data, subjective report of symptom relief, and lack of consistent dose of intrapericardial triamcinolone. Despite these limitations, the data suggest symptom resolution and reduced pericarditis recurrence with administration of intrapericardial triamcinolone to patients with autoreactive pericarditis. CONCLUSIONS: There is growing evidence that intrapericardial triamcinolone is safe and effective for the management of autoreactive pericarditis. The appropriate regimen (dose and duration of treatment), adverse effect profile, and specific therapeutic role require further investigation.

Antithrombotic therapy for the CardioWest temporary total artificial heart.

The CardioWest temporary total artificial heart serves as a viable bridge to orthotopic heart transplantation in patients who are experiencing end-stage refractory biventricular heart failure. This device is associated with a low, albeit still substantial, risk of thrombosis. Platelet interactions with artificial surfaces are complex and result in continuous activation of contact proteins despite therapeutic anticoagulation. We searched the medical literature (publication dates, January 1962-October 2009) in order to evaluate means of mitigating adverse events that have occurred after implantation of the CardioWest temporary total artificial heart.We conclude that the use of a multitargeted antithrombotic approach, involving anticoagulation (bivalirudin and warfarin) and antiplatelet therapy (dipyridamole and aspirin), can mitigate the procoagulative effects of mechanical circulatory assist devices, particularly those that are associated with the CardioWest temporary total artificial heart. Careful monitoring with use of a variant multisystem approach, involving efficacy tests (thrombelastography and light transmittance aggregometry), safety tests (laboratory analyses), and warfarin genomics, may maximize the therapeutic actions and minimize the bleeding risks that are associated with the multitargeted antithrombotic approach. The development and monitoring of individualized antithrombotic regimens require that informed health professionals appreciate the complexities and grasp the hazards that are associated with these therapies.