Delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage continues to be associated with high levels of morbidity and mortality. This complication had long been thought to occur secondary to severe cerebral vasospasm, but expert opinion now favors a multifactorial etiology, opening the possibility of new therapies. To date, no definitive treatment option for DCI has been recommended as standard of care, highlighting a need for further research into potential therapies. Milrinone has been identified as a promising therapeutic agent for DCI, possessing a mechanism of action for the reversal of cerebral vasospasm as well as potentially anti-inflammatory effects to treat the underlying etiology of DCI. Intra-arterial and intravenous administration of milrinone has been evaluated for the treatment of DCI in single-center case series and cohorts and appears safe and associated with improved clinical outcomes. Recent results have also brought attention to the potential outcome benefits of early, more aggressive dosing and titration of milrinone. Limitations exist within the available data, however, and questions remain about the generalizability of results across a broader spectrum of patients suffering from DCI. The development of a standardized protocol for milrinone use in DCI, specifically addressing areas requiring further clarification, is needed. Data generated from a standardized protocol may provide the impetus for a multicenter, randomized control trial. We review the current literature on milrinone for the treatment of DCI and propose a preliminary standardized protocol for further evaluation of both safety and efficacy of milrinone.
Aim: To discuss two patient cases of Serratia marcescens endocarditis and the paucity of literature regarding treatment options. Presentation of Case: Patient 1 was a 29-year old male who presented with native mitral valve Serratia marcescens endocarditis presumed secondary to intravenous drug use. He was empirically treated with vancomycin and piperacillin/tazobactam then transitioned to meropenem and gentamicin 1 mg/kg every 8 hours. He was maintained on vancomycin monotherapy for days 4-14. Gentamicin was restarted on hospital day 14 at 7 mg/kg every 36 hours for 6 weeks. He underwent mitral valve replacement on hospital day 20. He was readmitted on day 42 with splenic lesions and enlarging mycotic aneurysms. Patient 2 was a 38-year old male with native aortic valve Serratia marcescens endocarditis with septic emboli presumed secondary to intravenous drug use. He was treated with vancomycin and cefepime then was transitioned to ceftriaxone and levofloxacin. The patient underwent aortic valve replacement on hospital day 3 and was transitioned to meropenem and levofloxacin for 6 weeks. Discussion: The treatment strategies for both patients demonstrates that the optimal treatment strategy for Serratia marcescens endocarditis remains unclear. The gentamicin dosing for patient 1 demonstrates “synergy” and extended-interval dosing. Despite both dosing strategies being used, the patient continued to exhibit complications of the infection. Patient 2 demonstrates successful treatment of the infection with surgical intervention and a carbapenem/fluoroquinolone regimen. Conclusion: These cases demonstrates that much remains unclear in the treatment of Serratia marcescens endocarditis and more studies and case reports are needed.
Local anesthetics are used with neuraxial and regional techniques to provide pain relief, most commonly postoperatively. Each agent is a sodium-channel blocker, although each agent differs in onset of action, potency, duration of action, and safety profile. Chemical structure and lipophilicity are the main determinants of these characteristics. The agents may be used alone or in combination with an additive which alters the local anesthetic’s properties . Clinically, local anesthetics provide pain relief in a multimodal approach. This reduces opiate consumption, opiate-related adverse effects, and length of stay. Additional benefits when using neuraxial techniques include decreases in mortality, venous thromboembolism, myocardial infarction, pneumonia, respiratory depression, and duration of ileus. Although there are many adverse effects, the most serious include neurologic and cardiovascular. Seizures and cardiac arrest may result from local anesthetic systemic toxicity when systemic levels are elevated or the patient is predisposed. Dose adjustment, removal, or reversal of the agent may be clinically indicated. Lipid emulsion therapy is a reversal agent which acts as a sequestering vehicle for the local anesthetic. Liposomal bupivacaine, the newest formulation of local anesthetic, may provide an increased duration of action compared with standard formulations, although more evidence is needed. This review contains 5 figures, 5 tables, and 59 references. Keywords: amide, ester, epidural, local anesthetic, local anesthetic systemic toxicity, lipid emulsion therapy, liposomal bupivacaine, peripheral nerve block
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