Human factors and ergonomics to improve performance in intensive care units during the COVID-19 pandemic.

The COVID-19 pandemic has tested the very elements of human factors and ergonomics (HFE) to their maximum. HFE is an established scientific discipline that studies the interrelationship between humans, equipment, and the work environment. HFE includes situation awareness, decision making, communication, team working, leadership, managing stress, and coping with fatigue, empathy, and resilience. The main objective of HF is to optimise the interaction of humans with their work environment and technical equipment in order to maximise patient safety and efficiency of care. This paper reviews the importance of HFE in helping intensivists and all the multidisciplinary ICU teams to deliver high-quality care to patients in crisis situations.

Intra-abdominal hypertension, fluid balance, and adverse outcomes after orthotopic liver transplantation.

BACKGROUND: Intra-abdominal hypertension (IAH) is frequently encountered in critically ill surgical patients. We aimed to evaluate the incidence of IAH after orthotopic liver transplant (OLT) and its impact on organ function, hospital length-of-stay (LOS), and death. METHODS: This prospective, observational, cohort study evaluated consecutive adult patients admitted in the ICU after undergoing OLT. Intra-abdominal pressure (IAP) was measured every 4-6 h for 3 days. Worsening IAP was defined as a gradual increase in IAP over a period of time. Daily fluid balance was the daily sum of all intakes minus the output. RESULTS: IAH was observed in 48% of the patients within the first 3 days after ICU admission, while ACS was diagnosed in 15%. Patients with IAH had a higher positive fluid balance at day 1 (1764 mL [812-2733 mL] vs. 1301 mL [241-1904 mL], p = 0.025). Worsening IAH was associated with fewer days free of organ dysfunction. IAH within 72 h after ICU admission was independently associated with a composite outcome of death or a longer ICU LOS (odds ratio 2.9; CI 95% 1.02-8.25, p = 0.043). CONCLUSION: After OLT, nearly half of the patients presented IAH, that was associated with unfavorable outcomes.

A Natural History of Disease Framework for Improving the Prevention, Management, and Research on Post-viral Fatigue Syndrome and Other Forms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

We propose a framework for the treatment, rehabilitation, and research into Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) using a natural history of disease approach to outline the distinct disease stages, with an emphasis on cases following infection to provide insights into prevention. Moving away from the method of subtyping patients based on the various phenotypic presentations and instead reframing along the lines of disease progression could help with defining the distinct stages of disease, each of which would benefit from large prospective cohort studies to accurately describe the pathological mechanisms taking place therein. With a better understanding of these mechanisms, management and research can be tailored specifically for each disease stage. Pre-disease and early disease stages call for management strategies that may decrease the risk of long-term morbidity, by focusing on avoidance of further insults, adequate rest to enable recovery, and pacing of activities. Later disease stages require a more holistic and tailored management approach, with treatment-as this becomes available-targeting the alleviation of symptoms and multi-systemic dysfunction. More stringent and standardised use of case definitions in research is critical to improve generalisability of results and to create the strong evidence-based policies for management that are currently lacking in ME/CFS.

How Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Progresses: The Natural History of ME/CFS.

We propose a framework for understanding and interpreting the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) that considers wider determinants of health and long-term temporal variation in pathophysiological features and disease phenotype throughout the natural history of the disease. As in other chronic diseases, ME/CFS evolves through different stages, from asymptomatic predisposition, progressing to a prodromal stage, and then to symptomatic disease. Disease incidence depends on genetic makeup and environment factors, the exposure to singular or repeated insults, and the nature of the host response. In people who develop ME/CFS, normal homeostatic processes in response to adverse insults may be replaced by aberrant responses leading to dysfunctional states. Thus, the predominantly neuro-immune manifestations, underlined by a hyper-metabolic state, that characterize early disease, may be followed by various processes leading to multi-systemic abnormalities and related symptoms. This abnormal state and the effects of a range of mediators such as products of oxidative and nitrosamine stress, may lead to progressive cell and metabolic dysfunction culminating in a hypometabolic state with low energy production. These processes do not seem to happen uniformly; although a spiraling of progressive inter-related and self-sustaining abnormalities may ensue, reversion to states of milder abnormalities is possible if the host is able to restate responses to improve homeostatic equilibrium. With time variation in disease presentation, no single ME/CFS case description, set of diagnostic criteria, or molecular feature is currently representative of all patients at different disease stages. While acknowledging its limitations due to the incomplete research evidence, we suggest the proposed framework may support future research design and health care interventions for people with ME/CFS.

Influence of Sedation Level and Ventilation Status on the Diagnostic Validity of Delirium Screening Tools in the ICU-An International, Prospective, Bi-Center Observational Study (IDeAS).

Background and objectives: The use of delirium screening instruments (DSIs) is recommended in critical care practice for a timely detection of delirium. We hypothesize that the patient-related factors "level of sedation" and "mechanical ventilation" impact test validity of DSIs. Materials and Methods: This is a prospective, bi-center observational study (clinicaltrials.gov: NCT01720914). Critically ill patients were screened for delirium daily for up to seven days after enrollment using the Nursing Delirium Screening Scale (Nu-DESC), Intensive Care Delirium Screening Checklist (ICDSC), and Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Reference standard for delirium diagnosis was the neuropsychiatric examination using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Immediately before delirium assessment, ventilation status and sedation levels were documented. Results: 160 patients were enrolled and 151 patients went into final analysis. Delirium incidence was 23.2%. Nu-DESC showed a sensitivity and specificity of 88.5%, a positive predictive value (PPV) of 71.9%, and a negative predictive value (NPV) of 95.8%. ICDSC had a sensitivity of 62.5%, a specificity of 92.4%, a PPV of 71.4%, and a NPV of 89.0%. CAM-ICU showed a sensitivity of 75.0%, a specificity of 94.7%, a PPV of 85.7%, and a NPV of 90.0%. For Nu-DESC and ICDSC, test validity was significantly better for non-sedated patients (Richmond Agitation Sedation Scale (RASS) 0/-1), whereas test validity for CAM-ICU in a severity scale version showed no significant differences for different sedation levels. No DSI showed a significant difference in test validity between noninvasively and invasively ventilated patients. Conclusions: Test validities of DSIs were comparable to previous studies. The observational scores ICDSC and Nu-DESC showed a significantly better performance in awake and drowsy patients (RASS 0/-1) when compared with other sedation levels. Physicians should refrain from sedation whenever possible to avoid suboptimal performance of DSIs.

Pulmonary complications after non-cardiac surgeries: temporal patterns and risk factors.

BACKGROUND: Postoperative complications are the primary determinants of survival following major surgery. We aimed to characterize the early perioperative risk factors for postoperative pulmonary complications (POPCs) in patients undergoing major non-cardiac surgeries. METHODS: This study utilized a multicenter prospective observational cohort design. Adult patients undergoing non-cardiac surgeries and admitted to 21 Brazilian ICUs were screened for inclusion in the study. POPCs were defined as the presence of acute pulmonary oedema, nosocomial pneumonia, and extubation failure in the postoperative period. RESULTS: Of the 581 patients enrolled, 110 (19%) had at least one POPC, of whom 5% had acute pulmonary oedema, 10% extubation failure while 10% had pneumonia. Most cases of pulmonary oedema occurred in the first week after surgery, while pneumonia was more frequently a later occurrence. The mortality rate was significantly higher in the group with POPCs compared to the group of patients without POPCs (62% vs. 11%, RR: 5.1, 95% CI: 4.23-7.69; P < 0.001). A low functional capacity (RR: 4.6, 95% CI: 2.1-10.0), major surgery (RR: 3.6, 95% CI: 1.2-10.7), preoperative hemodynamic instability (RR: 3.4, 95% CI: 1.1-10.6), alcoholism (RR: 3.3, 95% CI: 1.0-10.7), unplanned surgery (RR: 2.3, 95% CI: 1.0-5.2), the SOFA score (RR: 1.1, 95% CI: 1.0-1.2), and increased central venous pressure (RR: 1.1, 95% CI: 1.0-1.1) were independent predictors of POPCs. CONCLUSIONS: Pulmonary complications are common in intensive care units after major non-cardiac surgeries. Awareness of the risk factors for POPCs may help multidisciplinary teams develop strategies to prevent these complications.

Early determinants of death due to multiple organ failure after noncardiac surgery in high-risk patients.

BACKGROUND: Prediction of perioperative cardiac complications is important in the medical management of patients undergoing noncardiac surgery. However, these patients frequently die as a consequence of primary or secondary multiple organ failure (MOF), often as a result of sepsis. We investigated the early perioperative risk factors for in-hospital death due to MOF in surgical patients. METHODS: This was a prospective, multicenter, observational cohort study performed in 21 Brazilian intensive care units (ICUs). Adult patients undergoing noncardiac surgery who were admitted to the ICU within 24 hours after operation were evaluated. MOF was characterized by the presence of at least 2 organ failures. To determine the relative risk (RR) of in-hospital death due to MOF, we performed a logistic regression multivariate analysis. RESULTS: A total of 587 patients were included (mean age, 62.4 ± 17 years). ICU and hospital mortality rates were 15% and 20.6%, respectively. The main cause of death was MOF (53%). Peritonitis (RR 4.17, 95% confidence interval [CI] 1.38-12.6), diabetes (RR 3.63, 95% CI 1.17-11.2), unplanned surgery (RR 3.62, 95% CI 1.18-11.0), age (RR 1.04, 95% CI 1 0.01-1.08), and elevated serum lactate concentrations (RR 1.52, 95% CI 1.14-2.02), a high central venous pressure (RR 1.12, 95% CI 1.04-1.22), a fast heart rate (RR 3.63, 95% CI 1.17-11.2) and pH (RR 0.04, 95% CI 0.0005-0.38) on the day of admission were independent predictors of death due to MOF. CONCLUSIONS: MOF is the main cause of death after surgery in high-risk patients. Awareness of the risk factors for death due to MOF may be important in risk stratification and can suggest routes for therapy.

The effects of vasoactive drugs on intestinal functional capillary density in endotoxemic rats: intravital video-microscopy analysis.

BACKGROUND: The use of vasoactive drugs to restore arterial blood pressure in patients with septic shock remains a cornerstone of intensive care medicine. However, vasopressors can accentuate the hypoperfusion of the gut during septic shock, allowing bacterial translocation and endotoxemia. In this study, we compared the effects of different vasoactive drugs on intestinal microcirculation and tissue oxygenation, independent of the effects of fluid therapy, in a rat model of endotoxemic shock. METHODS: Pentobarbital-anesthetized Wistar Kyoto rats were submitted to endotoxemic shock induced by Escherichia coli lipopolysaccharide (2 mg/kg IV). Arterial blood pressure was normalized by a continuous infusion of different vasoactive drugs, including epinephrine, norepinephrine, phenylephrine, dopamine, dobutamine, or a combination of dobutamine and norepinephrine. The functional capillary density (FCD) of the muscular layer of the small intestine was evaluated by intravital video-microscopy. Mesenteric venous blood gases and lactate concentrations were also analyzed. RESULTS: FCD decreased by approximately 25% to 60% after the IV infusion of epinephrine, norepinephrine, and phenylephrine. Administration of dopamine, dobutamine, and the combination of dobutamine and norepinephrine did not induce significant alterations in gut FCD. In addition, the mesenteric venous lactate concentration increased in the presence of phenylephrine and showed a tendency to increase after the administration of epinephrine and norepinephrine, whereas there was no observable increase after the administration of dopamine, dobutamine, and the combination of dobutamine with norepinephrine. CONCLUSION: This study confirms dissociation of the systemic hemodynamic and microvascular alterations in an experimental model of septic shock. Moreover, the results indicate that the use of dopamine, dobutamine, and dobutamine in combination with norepinephrine yields a protective effect on the microcirculation of the intestinal muscular layer in endotoxemic rats.

Epidemiologia e desfecho de pacientes cirúrgicos não cardíacos em unidades de terapia intensiva no Brasil / Epidemiology and outcomes of non-cardiac surgical patients in Brazilian intensive care units

OBJETIVO: Devido aos avanços da medicina e ao envelhecimento da população, a proporção de pacientes em risco de morte após cirurgias está aumentando. Nosso objetivo foi avaliar o desfecho e a epidemiologia de cirurgias não cardíacas em pacientes admitidos em unidade de terapia intensiva. MÉTODOS: Estudo prospectivo, observacional, de coorte, realizado em 21 unidades de terapia intensiva. Um total de 885 pacientes adultos, cirúrgicos, consecutivamente admitidos em unidades de terapia intensiva no período de abril a junho de 2006 foi avaliado e destes, 587 foram incluídos. Os critérios de exclusão foram; trauma, cirurgias cardíacas, neurológicas, ginecológicas, obstétricas e paliativas. Os principais desfechos foram complicações pós-cirúrgicas e mortalidade na unidade de terapia intensiva e 90 dias após a cirurgia. RESULTADOS: Cirurgias de grande porte e de urgência foram realizadas em 66,4 por cento e 31,7 por cento, dos pacientes, respectivamente. A taxa de mortalidade na unidade de terapia intensiva foi de 15 por cento, e 38 por cento dos pacientes tiveram complicações no pós-operatório. A complicação mais comum foi infecção ou sepse (24,7 por cento). Isquemia miocárdica foi diagnosticada em apenas 1,9 por cento. Um total de 94 por cento dos pacientes que morreram após a cirurgia tinha co-morbidades associadas (3,4 ± 2,2). A principal causa de óbito foi disfunção de múltiplos órgãos (53 por cento). CONCLUSÃO: Sepse é a causa predominante de morbidade em pacientes submetidos a cirurgias não cardíacas. A grande maioria dos óbitos no pós-operatório ocorreu por disfunção de múltiplos órgãos.

OBJECTIVES: Due to the dramatic medical breakthroughs and an increasingly ageing population, the proportion of patients who are at risk of dying following surgery is increasing over time. The aim of this study was to evaluate the outcomes and the epidemiology of non-cardiac surgical patients admitted to the intensive care unit. METHODS: A multicenter, prospective, observational, cohort study was carried out in 21 intensive care units. A total of 885 adult surgical patients admitted to a participating intensive care unit from April to June 2006 were evaluated and 587 patients were enrolled. Exclusion criteria were trauma, cardiac, neurological, gynecologic, obstetric and palliative surgeries. The main outcome measures were postoperative complications and intensive care unit and 90-day mortality rates. RESULTS: Major and urgent surgeries were performed in 66.4 percent and 31.7 percent of the patients, respectively. The intensive care unit mortality rate was 15 percent, and 38 percent of the patients had postoperative complications. The most common complication was infection or sepsis (24.7 percent). Myocardial ischemia was diagnosed in only 1.9 percent of the patients. A total of 94 percent of the patients who died after surgery had co-morbidities at the time of surgery (3.4 ± 2.2). Multiple organ failure was the main cause of death (53 percent). CONCLUSION: Sepsis is the predominant cause of morbidity in patients undergoing non-cardiac surgery. In this patient population, multiple organ failure prevailed as the most frequent cause of death in the hospital.

Lipopolysaccharide binding protein in a surgical intensive care unit: a marker of sepsis?

OBJECTIVES: We investigated the time course of lipopolysaccharide binding protein (LBP) plasma concentrations in patients in the surgical intensive care unit (ICU), their value in discriminating sepsis from systemic inflammatory response syndrome, and their association with severity of sepsis and outcome in these patients compared with interleukin (IL)-6, C-reactive protein, and procalcitonin. DESIGN: Prospective, observational, cohort study. SETTING: Academic ICU. PATIENTS: All 327 consecutively admitted patients. MEASUREMENTS AND MAIN RESULTS: Serum LBP concentrations were higher in patients who had severe sepsis/septic shock on ICU admission than in patients who never had sepsis (20.5 [8.1-38.8] vs. 14.2 [7.7-22.2] microg/mL, p < .05) but were similar in patients with sepsis without organ failure and those who never had sepsis. After 3 days, LBP levels were similar in all groups. In a receiver operating characteristic curve analysis, LBP concentrations moderately discriminated sepsis from systemic inflammatory response syndrome (area under curve [AUC] = .66) and severe sepsis from sepsis without organ failure (AUC = .71). IL-6 had the highest AUC in discriminating sepsis from other conditions (AUC = .76) and procalcitonin had the highest AUC for discrimination of severe sepsis from sepsis (AUC = .86). LBP concentrations on admission and during the first week were similar in patients with gram-positive and those with gram-negative infections (15.9 [11-26.7] and 37.2 [25.1-62.4] vs. 16.3 [5.3-31.6] and 31.6 [13.4], microg/mL, p > .2). LBP concentrations on admission were similar in nonsurvivors and survivors and did not discriminate ICU mortality. However, the maximum LBP concentration during the first 3 days in the ICU discriminated moderately between survivors and nonsurvivors. CONCLUSIONS: In the surgical ICU, LBP moderately discriminated patients without infection from patients with severe sepsis but not from patients with sepsis without organ dysfunction. LBP concentrations did not distinguish between gram-positive and gram-negative infections. The correlation of LBP concentrations with disease severity and outcome is weak compared with other markers and its use as a biomarker is not warranted in this patient population.

Epidemiology and outcomes of non-cardiac surgical patients in Brazilian intensive care units. / Epidemiologia e desfecho de pacientes cirúrgicos não cardíacos em unidades de terapia intensiva no Brasil.

OBJECTIVES: Due to the dramatic medical breakthroughs and an increasingly ageing population, the proportion of patients who are at risk of dying following surgery is increasing over time. The aim of this study was to evaluate the outcomes and the epidemiology of non-cardiac surgical patients admitted to the intensive care unit. METHODS: A multicenter, prospective, observational, cohort study was carried out in 21 intensive care units. A total of 885 adult surgical patients admitted to a participating intensive care unit from April to June 2006 were evaluated and 587 patients were enrolled. Exclusion criteria were trauma, cardiac, neurological, gynecologic, obstetric and palliative surgeries. The main outcome measures were postoperative complications and intensive care unit and 90-day mortality rates. RESULTS: Major and urgent surgeries were performed in 66.4% and 31.7% of the patients, respectively. The intensive care unit mortality rate was 15%, and 38% of the patients had postoperative complications. The most common complication was infection or sepsis (24.7%). Myocardial ischemia was diagnosed in only 1.9% of the patients. A total of 94 % of the patients who died after surgery had co-morbidities at the time of surgery (3.4 ± 2.2). Multiple organ failure was the main cause of death (53%). CONCLUSION: Sepsis is the predominant cause of morbidity in patients undergoing non-cardiac surgery. In this patient population, multiple organ failure prevailed as the most frequent cause of death in the hospital.

Coagulação intravascular disseminada no paciente crítico / Coagulation intravascular disseminated in critical patient

Coagulação intravascular disseminada é uma síndrome caracterizada por ativação sistêmica da coagulação, com conseqüente deposição intravascular de fibrina, trombose vascular e disfunção de órgão. O consumo de plaquetas e fatores de coagulação provoca trombocitopenia e sangramentos. O principal fator etiológico no paciente grave é a sepse. O tratamento consiste em tratar a causa e repor hemoderivados se houver sangramento ou algum procedimento cirúrgico for programado.

Antibioticoterapia para infecções por bactérias gram-positivas no paciente grave / Antibioticotherapy for gram-positive bacteria infections in serious patient

O aumento importante do número de infecções causadas por bactérias Gram-positivas e o surgimento de resistência aos antibióticos destinados a tratar estas infecções são motivos de preocupação das autoridades internacionais em infecção hospitalar. O presente artigo tem como objetivo revisar os principais antibióticos utilizados para o tratamento destes agentes, como oxacilina, vancomicina, teicoplanina, linezolida, quinupristina-dalfopristina, daptomicina e tigeciclina.

Delirium em pacientes críticos: [revisão] / Delirium in the critically ill patient~: [review]

JUSTIFICATIVA E OBJETIVOS: O delirium é um achado freqüente em pacientes críticos. Apesar de estar associado a um aumento da morbidade e mortalidade, ainda é pouco reconhecido pelos intensivistas. Esta revisão teve como objetivo revisar os principais aspectos relacionados ao delirium no paciente critico. CONTEÚDO: Definição, incidência, mortalidade, fatores de risco, fisiopatologia, diagnóstico e tratamento do delirium no paciente crítico. CONCLUSÕES: O delirium é um distúrbio da consciência, cognição e percepção que pode acometer até 80 por cento dos pacientes em ventilação mecânica. Os fatores de risco incluem doenças sistêmicas agudas, idade avançada, distúrbios cognitivos preexistentes, privação do sono e certas medicações, como os fármacos com atividade anticolinérgica. Embora novas ferramentas estejam disponíveis para o seu rápido diagnóstico em pacientes críticos, os profissionais de saúde ainda não costumam monitorizar esta condição. Nos últimos anos a prevenção e o diagnóstico têm sido priorizados. O haloperidol continua sendo a medicação de escolha embora exista alguma evidência da eficácia da risperidona.

BACKGROUND AND OBJECTIVES: Delirium is a frequent finding in the critically ill patient. Although it is associated with increased morbidity and mortality, it is often not recognized by intensive care doctors. This review will address the main issues regarding delirium in critically ill patients. CONTENTS: Definition, incidence, mortality, risk factors, diagnosis, and treatment of delirium in the critically ill. CONCLUSIONS: Deliriumis defined as a disturbance of consciousness, attention, cognition and perception that occurs frequently in critically ill patients. It occurs in as many as 80 percent of mechanically ventilated ICU patients. Risk factors for delirium include acute systemic illnesses, older age, pre-existing cognitive impairment, sleep deprivation, and medications with anticholinergic activity. Although new assessment tools are available for rapidly and accurately measuring deliriumin critically ill patients, healthcare professionals still do not regularly monitor for this condition. In recent years, the emphasis in the approach to delirium has shifted to systematic screening and prevention. Haloperidol remains the standard treatment for delirium, but there is some evidence for the efficacy of risperidone.

[Delirium in the critically ill patient]. / Delirium em pacientes críticos.

BACKGROUND AND OBJECTIVES: Delirium is a frequent finding in the critically ill patient. Although it is associated with increased morbidity and mortality, it is often not recognized by intensive care doctors. This review will address the main issues regarding delirium in critically ill patients. CONTENTS: Definition, incidence, mortality, risk factors, diagnosis, and treatment of delirium in the critically ill. CONCLUSIONS: Deliriumis defined as a disturbance of consciousness, attention, cognition and perception that occurs frequently in critically ill patients. It occurs in as many as 80% of mechanically ventilated ICU patients. Risk factors for delirium include acute systemic illnesses, older age, pre-existing cognitive impairment, sleep deprivation, and medications with anticholinergic activity. Although new assessment tools are available for rapidly and accurately measuring deliriumin critically ill patients, healthcare professionals still do not regularly monitor for this condition. In recent years, the emphasis in the approach to delirium has shifted to systematic screening and prevention. Haloperidol remains the standard treatment for delirium, but there is some evidence for the efficacy of risperidone.

Depressão miocárdica na sepse / Myocardial depression in sepsis

A disfunção miocárdica é um evento reconhecido na sepse e no choque séptico há muitos anos. Diversos mecanismos foram propostos, como a isquemia global do músculo cardíaco e a liberação de mediadores inflamatórios com propriedades depressoras miocárdicas pelos macrófagos tissulares. O mecanismo de ação destes mediadores também foi extensamente estudado, sugerindo serem o óxido nítrico e a esfingosina os efetores da disfunção mediada pelo TNF-a e pela IL-1B. O tratamento específico da disfunção miocárdica na sepse e no choque séptico ainda não foi encontrado, porém sabe-se que a mesma é reversível após o controle da doença de base

The myocardial dysfunction is a well known event in sepsis and septic shock. Many mechanisms were proposed such as global ischemia of the cardiac muscle and the inflammatory mediators production leading to myocardial depression. The mechanism of action of these mediators has also been studied. Nitric oxide and esfingosin are possible effectors of the dysfunction that is mediated by TNF-a and IL-1B. The specific treatment of the myocardial dysfunction in sepsis and septic shock has not been defined. The heart function improves after the control of the disease

Massive nasal bleeding and hemodynamic instability associated with clopidogrel.

A 58-year-old woman was brought to our emergency department with massive nasal bleeding and hemodynamic instability. The patient had been on clopidogrel treatment (75 mg/day) for 2 years, which was started after an episode of transitory ischemic attack. Blood pressure normalized following the administration of intravenous fluids, and the bleeding stopped after nasal tamponade and desmopressin therapy.