RESUMEN
The intensive care unit (ICU) is a finite and expensive resource with demand not infrequently exceeding capacity. Understanding ICU capacity strain is essential to gain situational awareness. Increased capacity strain can influence ICU triage decisions, which rely heavily on clinical judgment. Having an admission and triage protocol with which clinicians are very familiar can mitigate difficult, inappropriate admissions. This article reviews these concepts and methods of in-hospital triage.
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Unidades de Cuidados Intensivos , Triaje , Triaje/métodos , Humanos , Unidades de Cuidados Intensivos/organización & administración , HospitalizaciónRESUMEN
BACKGROUND Listeria monocytogenes is known to cause meningitis, bacteremia, and rhabdomyolysis, typically associated with acute kidney injury. We present the case of a young woman who developed severe rhabdomyolysis without kidney failure in the setting of listeriosis. CASE REPORT A 22-year-old woman with a past medical history of type 1 diabetes mellitus presented with fever, headache, and vomiting. Initial blood work revealed a white blood cell count of 22 K/µL, creatine phosphokinase (CPK) level of 275 U/L, blood urea nitrogen of 9 mg/dL, and creatinine of 0.89 mg/dL. A lumbar puncture (LP) was performed and was positive for Listeria monocytogenes. Her initial point-of-care ultrasound demonstrated hyperdynamic left ventricular (LV) function. Although she was immediately started on empiric coverage for bacterial and viral meningitis with intravenous vancomycin, ceftriaxone, and acyclovir, the antimicrobial regimen was changed to ampicillin and gentamicin after the LP results were obtained. On the second hospital day, a repeat echocardiogram demonstrated a dilated LV with severely reduced function with an ejection fraction (EF) of 30%. Her CPK increased and peaked at 299 637 U/L by day 6. Despite the low EF and elevated CPK, her kidney function remained at baseline at all times. Her EF improved to 60% by hospital day 20. She received large volumes of intravenous fluids, completed a 3-week course of ampicillin, continued to improve, and was discharged to a rehabilitation facility with no deficits. CONCLUSIONS Listeria infection can be associated with severe rhabdomyolysis, which is usually associated with kidney dysfunction. Administration of large volumes of intravenous fluids may decrease this likelihood.
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Meningitis por Listeria , Rabdomiólisis , Femenino , Humanos , Adulto Joven , Adulto , Meningitis por Listeria/complicaciones , Meningitis por Listeria/diagnóstico , Rabdomiólisis/complicaciones , Ampicilina , Vancomicina , Riñón/fisiologíaRESUMEN
PURPOSE: Montefiore Medical Center (MMC) in the Bronx, New York, was subjected to an unprecedented surge of critically ill patients with COVID-19 disease during the initial outbreak of the pandemic in New York State in the spring of 2020. It is important to describe our experience in order to assist hospitals in other areas of the country that may soon be subjected to similar surges. MATERIALS AND METHODS: We retrospectively reviewed the expansion of critical care medicine services at Montefiore during the COVID-19 surge in terms of space, staff, stuff, and systems. In addition, we report on a debriefing session held with a multidisciplinary group of frontline CCM providers at Montefiore. FINDINGS: The surge of critically ill patients from COVID-19 disease necessitated a tripling of critical care bed capacity at (MMC), with attendant increased needs for staffing, equipment, and systematic innovations to increase efficiency and effectiveness. Feedback from a multidisciplinary group of frontline providers revealed multiple opportunities for improvement for the next potential surge at MMC as well as guidance for other hospitals. CONCLUSIONS: Given increasing cases and burden of critical illness from COVID-19 across the US, engineering safe and effective expansions of critical care capacity will be crucial. We hope that our description of what worked and what did not at MMC will help guide other hospitals in their pandemic preparedness.
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COVID-19/epidemiología , COVID-19/terapia , Cuidados Críticos , Enfermedad Crítica/epidemiología , Enfermedad Crítica/terapia , Unidades de Cuidados Intensivos/organización & administración , Femenino , Humanos , Masculino , Ciudad de Nueva York/epidemiología , Pandemias , Estudios Retrospectivos , SARS-CoV-2RESUMEN
In continuation of our efforts to discover novel nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) as potentially "Safe NSAIDs," we report herein the design, synthesis and evaluation of 21 new NO-NSAIDs of commonly used NSAIDs such as aspirin, diclofenac, naproxen, flurbiprofen, ketoprofen, sulindac, ibuprofen and indomethacin. These prodrugs have NO-releasing disulfide linker attached to a parent NSAID via linkages such as an ester (compounds 9-16), a double ester (compounds 17-24), an imide (compounds 25-30) or an amide (compounds 31-33). Among these NO-NSAIDs, the ester-containing NO-aspirin (9), NO-diclofenac (10), NO-naproxen (11), and the imide-containing NO-aspirin (25), NO-flurbiprofen (27) and NO-ketoprofen (28) have shown promising oral absorption, anti-inflammatory activity and NO-releasing property, and also protected rats from NSAID-induced gastric damage. NO-aspirin compound 25, on further co-evaluation with aspirin at equimolar doses, exhibited comparable dose-dependent pharmacokinetics, inhibition of gastric mucosal prostaglandin E(2) (PGE(2)) synthesis and analgesic properties to those of aspirin, but retained its gastric-sparing properties even after doubling its oral dose. These promising NO-NSAIDs could therefore represent a new class of potentially "Safe NSAIDs" for the treatment of arthritic pain and inflammation.
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Antiinflamatorios no Esteroideos/química , Óxido Nítrico/metabolismo , Profármacos/química , Amidas/síntesis química , Amidas/química , Animales , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/farmacocinética , Área Bajo la Curva , Diseño de Fármacos , Ésteres , Imidas/síntesis química , Imidas/química , Masculino , Profármacos/síntesis química , Profármacos/farmacocinética , Ratas , Ratas Sprague-Dawley , Ratas WistarRESUMEN
Numerous publications have reported the significant pharmacodynamic activity of Curcumin (CRM) despite low or undetectable levels in plasma. The objective of the present study was to perform a detailed pharmacokinetic evaluation of CRM after the oral administration of a highly bioavailable lipidic formulation of CRM (CRM-LF) in human subjects. Cmax, Tmax and AUC0-¥ were found to be 183.35 ± 37.54 ng/mL, 0.60 ± 0.05 h and 321.12 ± 25.55 ng/mL respectively, at a dose of 750 mg. The plasma profile clearly showed three distinct phases, viz., absorption, distribution and elimination. A close evaluation of the primary pharmacokinetic parameters provided valuable insight into the behavior of the CRM after absorption by CRM-LF. CRM-LF showed a lag time (Tlag) of 0.18 h (around 12 min). Pharmacokinetic modeling revealed that CRM-LF followed a two-compartment model with first order absorption, lag time and first order elimination. A high absorption rate constant (K01, 4.51/h) signifies that CRM-LF ensured rapid absorption of the CRM into the central compartment. This was followed by the distribution of CRM from the central to peripheral compartment (K12, 2.69/h). The rate of CRM transfer from the peripheral to central compartment (K21, 0.15/h) was slow. This encourages higher tissue levels of CRM as compared with plasma levels. The study provides an explanation of the therapeutic efficacy of CRM, despite very low/undetectable levels in the plasma.
RESUMEN
The present study was designed to evaluate, P2026 [(2-((2-(nitrooxy)ethyl)disulfanyl)ethyl 2-(2-(2,6-dichlorophenylamino)phenyl)acetate)], a novel NO (nitric oxide) donor prodrug of diclofenac for its ability to release NO and diclofenac, and whether P2026 provides advantage of improved activity/gastric tolerability over diclofenac. Oral bioavailability of P2026 was estimated from plasma concentration of diclofenac and nitrate/nitrite (NOx). Anti-inflammatory activity was evaluated in three different models of inflammation: acute (carrageenan-induced paw oedema), chronic (adjuvant-induced arthritis), and systemic (lipopolysaccharide-induced endotoxic shock). Gastric tolerability was evaluated from compound's propensity to cause gastric ulcers. P2026 exhibited dose-dependent diclofenac and NOx release. Similar to diclofenac, P2026 showed potent anti-inflammatory activity in acute and chronic model, whereas it improved activity in systemic model. Both diclofenac and P2026 inhibited gastric prostaglandin, but only diclofenac produced dose-dependent haemorrhagic ulcers. Thus, the results suggest that coupling of NO and diclofenac contribute to improved gastric tolerability while retaining the anti-inflammatory properties of diclofenac.
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Antiinflamatorios no Esteroideos/farmacología , Diclofenaco/análogos & derivados , Inflamación/tratamiento farmacológico , Nitratos/administración & dosificación , Nitratos/farmacología , Donantes de Óxido Nítrico/farmacología , Profármacos/farmacología , Administración Oral , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacocinética , Antiinflamatorios no Esteroideos/toxicidad , Artritis Experimental/tratamiento farmacológico , Disponibilidad Biológica , Inhibidores de la Ciclooxigenasa/administración & dosificación , Inhibidores de la Ciclooxigenasa/farmacocinética , Inhibidores de la Ciclooxigenasa/farmacología , Inhibidores de la Ciclooxigenasa/toxicidad , Diclofenaco/administración & dosificación , Diclofenaco/farmacocinética , Diclofenaco/farmacología , Diclofenaco/toxicidad , Dinoprostona/biosíntesis , Evaluación Preclínica de Medicamentos , Epoprostenol/biosíntesis , Mucosa Gástrica/metabolismo , Masculino , Nitratos/farmacocinética , Nitratos/toxicidad , Óxido Nítrico/metabolismo , Donantes de Óxido Nítrico/administración & dosificación , Donantes de Óxido Nítrico/farmacocinética , Donantes de Óxido Nítrico/toxicidad , Profármacos/administración & dosificación , Profármacos/farmacocinética , Profármacos/toxicidad , Ratas , Ratas Sprague-Dawley , Estómago/efectos de los fármacos , Úlcera Gástrica/inducido químicamenteRESUMEN
Recently, a new class of nitric-oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) is being studied as 'Safe NSAIDs' because of their gastric-sparing properties. As an extension of our novel disulfide linker technology, we have designed, synthesized and evaluated novel NO-releasing NSAID prodrugs such as NO-Aspirin (1b-d) and NO-Diclofenac (2b-c). Although the amide-containing derivative 1d did not show any bioavailability, the remaining compounds have shown fair to excellent pharmacokinetic, anti-inflammatory and gastric-sparing properties. Among them, however, the NO-Diclofenac (2b) has shown the most promising pharmacokinetic, anti-inflammatory and NO-releasing properties and protected rats from NSAID-induced gastric damage which could be attributable to the beneficial effects of NO released from these prodrugs.
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Antiinflamatorios no Esteroideos/farmacología , Aspirina/farmacología , Diclofenaco/farmacología , Óxido Nítrico/metabolismo , Profármacos/farmacología , Estómago/efectos de los fármacos , Animales , Antiinflamatorios no Esteroideos/química , Aspirina/química , Diclofenaco/química , Profármacos/química , RatasRESUMEN
OBJECTIVE: To review the current literature surrounding the history of bioterrorism, the relative risk of a bioterrorist attack, methods of surveillance for biological agents, identification and management of various biological agent casualties, as well as the role of the intensivist in managing a bioterrorist attack. METHODS: Internet and Medline search (from 1966 to 2004) for articles relating to bioterrorism, biological agents, biological warfare, hospital preparedness, disaster management, and intensive care. CONCLUSIONS: There are few instances of a successful large-scale biological weapons attack in history. Weaponization of biological agents for aerosol dispersal is difficult and has often proved to be the rate-limiting step for a successful attack. Although a successful biological attack is currently unlikely, it is still feasible. More importantly, the threat of one is likely to cause much panic in the public, while a successful attack would overburden the current healthcare infrastructure. Intensivists will need to have specific knowledge of identifying and managing casualties from various biological agents. In addition, they will need to play an integral part in the preparedness of their institutions and communities for managing a bioterrorist event.
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Bioterrorismo , Cuidados Críticos/organización & administración , Planificación en Desastres , Brotes de Enfermedades/prevención & control , Guerra Biológica/historia , Bioterrorismo/historia , Centers for Disease Control and Prevention, U.S./organización & administración , Control de Enfermedades Transmisibles/organización & administración , Enfermedades Transmisibles/diagnóstico , Enfermedades Transmisibles/terapia , Planificación en Desastres/historia , Monitoreo del Ambiente/métodos , Historia del Siglo XVIII , Historia del Siglo XIX , Historia del Siglo XX , Historia del Siglo XXI , Historia Medieval , Humanos , Vigilancia de la Población/métodos , Medición de Riesgo/organización & administración , Estados UnidosRESUMEN
A 44-year-old woman with a history of major depression and obsessive-compulsive disorder was prescribed mirtazapine. She came to the emergency department approximately 2 months after starting therapy; severe hypertriglyceridemia, acute pancreatitis, and diabetic ketoacidosis were diagnosed. Although these adverse effects have been reported in early clinical trials, we found only three published cases of subclinical pancreatitis possibly associated with mirtazapine therapy. We suspect that mirtazapine-associated hypertriglyceridemia had contributed to the development of acute pancreatitis and diabetic ketoacidosis in our patient. All these problems resolved with supportive care and discontinuation of mirtazapine. Her serum amylase, lipase, and lipid levels were normal 2 months after the acute event occurred. Health care providers should be aware of these possible adverse effects. Serum glucose and triglyceride levels should be measured at baseline and monitored regularly thereafter in all patients receiving mirtazapine therapy.
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Antidepresivos Tricíclicos/efectos adversos , Cetoacidosis Diabética/inducido químicamente , Hipertrigliceridemia/inducido químicamente , Mianserina/análogos & derivados , Mianserina/efectos adversos , Pancreatitis/inducido químicamente , Enfermedad Aguda , Adulto , Antidepresivos Tricíclicos/uso terapéutico , Trastorno Depresivo/complicaciones , Trastorno Depresivo/tratamiento farmacológico , Femenino , Humanos , Mianserina/uso terapéutico , Mirtazapina , Trastorno Obsesivo Compulsivo/complicaciones , Trastorno Obsesivo Compulsivo/tratamiento farmacológicoRESUMEN
A bioterrorist attack of any kind has the potential to overwhelm a community and, indeed, in the case of smallpox, an entire nation. During such an attack the number of patients requiring hospitalization and specifically critical care is likely to be enormous. Intensivists will be at the forefront of this war and will play an important role in dealing with mass casualties in an attempt to heal the community. A high degree of suspicion and prompt recognition of an event will be required to contain it. Specific knowledge of the possible agents that can be used will be key in managing patients and in estimating the needs of a health care facility and community to deal with the future course of events. Intensivists play various roles aside from the delivery of critical care to the patient in the ICU. These roles include making triage decisions regarding the appropriate use of critical care beds (which automatically dictates how other non-ICU beds are used and managed) and serving as a team member of ethics committees (on such issues as dying, futility, and withdrawal of care). Indeed, intensivists are no strangers to disaster management and have served on the forefront of many. A biologic weapons attack, however, is likely to push this multidimensional nature of the intensivist to the maximum, because such an attack is likely to result in a more homogeneous critically ill population where the number of critical care staff and supplies to treat the victims may be limited. One hopes that such an event will not occur. Sadly, however the events of September 11, 2001, have only heightened the awareness of such a possibility.