Cerebral Vasospasm After Subarachnoid Hemorrhage: Respective Short-Term Effects of Induced Arterial Hypertension and its Combination With IV Milrinone: A Proof-of-Concept Study Using Transcranial Doppler Ultrasound.

OBJECTIVES: It is unclear whether IV milrinone relaxes spasmed cerebral arteries and therefore reduces cerebral blood mean velocity (Vmean). In patients treated for cerebral vasospasm, we aimed to assess and delineate the respective impacts of induced hypertension and its combination with IV milrinone on cerebral hemodynamics as assessed with transcranial Doppler. DESIGN: Observational proof-of-concept prospective study. SETTING: ICU in a French tertiary care center. PATIENTS: Patients with aneurysmal subarachnoid hemorrhage who received induced hypertension (mean arterial blood pressure [MBP] of 100-120 mm Hg) and IV milrinone (0.5 µg/kg/min) for moderate-to-severe cerebral vasospasm. We excluded patients who underwent invasive angioplasty or milrinone discontinuation within 12 hours after the diagnosis of vasospasm. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Vmean was measured at vasospasm diagnosis (TDIAGNOSIS), after the induction of hypertension (THTN), and 1 (THTN+MILRINONE_H1) and 12 hours after the adjunction of IV milrinone (THTN+MILRINONE_H12). Thirteen patients were included. Median Vmean was significantly lower (p < 0.01) at THTN+MILRINONE_H1 (99 [interquartile range (IQR) 89; 134] cm.s-1) and THTN+MILRINONE_H12 (85 [IQR 73-127] cm/s) than at TDIAGNOSIS (136 [IQR 115-164] cm/s) and THTN (148 [IQR 115-183] cm/s), whereas TDIAGNOSIS and THTN did not significantly differ. In all patients but one, Vmean at THTN+MILRINONE_H1 was lower than its value at TDIAGNOSIS (p = 0.0005). Vmean-to-MBP and Vmean-to-cardiac output (CO) ratios (an assessment of Vmean regardless of the level of MBP [n = 13] or CO [n = 7], respectively) were, respectively, similar at TDIAGNOSIS and THTN but were significantly lower after the adjunction of milrinone (p < 0.01). CONCLUSIONS: The induction of arterial hypertension was not associated with a significant decrease in Vmean, whereas the adjunction of IV milrinone was, regardless of the level of MBP or CO. This suggests that IV milrinone may succeed in relaxing spasmed arteries.

Intravenous Milrinone for Cerebral Vasospasm in Subarachnoid Hemorrhage: The MILRISPASM Controlled Before-After Study.

BACKGROUND: Intravenous (IV) milrinone, in combination with induced hypertension, has been proposed as a treatment option for cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). However, data on its safety and efficacy are scarce. METHODS: This was a controlled observational study conducted in an academic hospital with prospectively and retrospectively collected data. Consecutive patients with cerebral vasospasm following aSAH and treated with both IV milrinone (0.5 µg/kg/min-1, as part of a strict protocol) and induced hypertension were compared with a historical control group receiving hypertension alone. Multivariable analyses aimed at minimizing potential biases. We assessed (1) 6-month functional disability (defined as a score between 2 and 6 on the modified Rankin Scale) and vasospasm-related brain infarction, (2) the rate of first-line or rescue endovascular angioplasty for vasospasm, and (3) immediate tolerance to IV milrinone. RESULTS: Ninety-four patients were included (41 and 53 in the IV milrinone and the control group, respectively). IV milrinone infusion was independently associated with a lower likelihood of 6-month functional disability (adjusted odds ratio [aOR] = 0.28, 95% confidence interval [CI] = 0.10-0.77]) and vasospasm-related brain infarction (aOR = 0.19, 95% CI 0.04-0.94). Endovascular angioplasty was less frequent in the IV milrinone group (6 [15%] vs. 28 [53%] patients, p = 0.0001, aOR = 0.12, 95% CI 0.04-0.38). IV milrinone (median duration of infusion, 5 [2-8] days) was prematurely discontinued owing to poor tolerance in 12 patients, mostly (n = 10) for "non/hardly-attained induced hypertension" (mean arterial blood pressure < 100 mmHg despite 1.5 µg/kg/min-1 of norepinephrine). However, this event was similarly observed in IV milrinone and control patients (n = 10 [24%] vs. n = 11 [21%], respectively, p = 0.68). IV milrinone was associated with a higher incidence of polyuria (IV milrinone patients had creatinine clearance of 191 [153-238] ml/min-1) and hyponatremia or hypokalemia, whereas arrhythmia, myocardial ischemia, and thrombocytopenia were infrequent. CONCLUSIONS: Despite its premature discontinuation in 29% of patients as a result of its poor tolerance, IV milrinone was associated with a lower rate of endovascular angioplasty and a positive impact on long-term neurological and radiological outcomes. These preliminary findings encourage the conduction of confirmatory randomized trials.

Evaluation of the impact of HMS Plus on postoperative blood loss compared with ACT Plus in cardiac surgery.

BACKGROUND: The standardized management of anticoagulation during the cardiopulmonary bypass seems inaccurate because of patients and surgeries variability. This study evaluates if an individualized management of heparin and protamine guided by the HMS Plus system during cardiopulmonary bypass could reduce postoperative blood loss. METHODS: We conducted a prospective, controlled, unblinded, single-center study. One-hundred and eighthy-eight patients operated for cardiac surgery were included. Patients were divided in ACT Plus group (standardized approach) and HMS Plus group (individualized approach). The primary outcome was blood-loss volume during the first 24 postoperative hours. The main secondary outcomes were the need for allogeneic blood transfusions and the final protamine/heparin ratio. RESULTS: There was no difference between the two groups for baseline characteristics. Medium blood-loss volume in the ACT Plus group was 522±260 mL vs. 527±255 mL in the HMS Plus group (P=0.58). The final protamine/heparin ratio in the ACT Plus group was 0.94±0.1 vs. 0.58±0.1 in the HMS Plus group (P<0.0001). The transfusion rate during surgery in the ACT Plus group was 25% vs. 14% in the HMS Plus group (P=0.09). CONCLUSIONS: HMS Plus did not reduce the mean blood-loss volume during the first 24 postoperative hours compared with ACT Plus. Its utility for potential transfusion rate reduction remains to be proven.

Mucormycosis in intensive care unit: surgery is a major prognostic factor in patients with hematological malignancy.

BACKGROUND: Mucormycosis is an invasive fungal infection, with an increasing incidence especially in patients with hematological malignancies. Its prognosis is poor because of its high invasive power and its intrinsic low susceptibility to antifungal agents. We aimed to describe the epidemiology of mucormycosis in intensive care units (ICU) and evaluate the outcomes. We performed a retrospective multi-center study in 16 French ICUs between 2008 and 2017. We compared the patients who survived in ICU and the patients who did not to identify factors associated with ICU survival. Then, we focused on the subgroup of patients with hematological malignancies. RESULTS: Mucormycosis was diagnosed in 74 patients during the study period. Among them, 60 patients (81%) were immunocompromised: 41 had hematological malignancies, 9 were solid organ transplant recipients, 31 received long-term steroids, 11 had diabetes, 24 had malnutrition. Only 21 patients survived to ICU stay (28.4%) with a median survival of 22 days (Q1-Q3 = 9-106) and a survival rate at day 28 and day 90, respectively, of 35.1% and 26.4%. Survivors were significantly younger (p = 0.001), with less frequently hematological malignancies (p = 0.02), and less malnutrition (p = 0.05). Median survival in patients with hematological malignancies (n = 41) was 15 days (Q1-Q3 = 5-23.5 days). In this subgroup, curative surgery was a major factor associated with survival in multivariate analysis (odds ratio = 0.71, [0.45-0.97], p < 0.001). CONCLUSION: Overall prognosis of mucormycosis in ICU remains poor, especially in patients with hematological malignancies. In this subgroup of patients, a therapeutic strategy including curative surgery was the main factor associated with survival.

Oenantha Crocata: A Case Report of Multiple Poisoning with Fatal Outcome.

BACKGROUND: Plant poisonings are uncommon in adults, and rarely fatal. Oenantha crocata is a toxic plant growing in the humid grasslands of North America and Western Europe. CASE REPORT: We report here two adults who ingested Oenantha crocata roots, having mistaken them for edible tuberous radish. One developed vomiting and needed only 24 h symptomatic treatment, whereas the other suffered prolonged convulsions, cardiac arrest, and severe metabolic acidosis, leading to a fatal outcome. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Cases of poisoning with Oenantha crocata are rare and destabilizing. With increased interest in "natural" foods and team building by survival training, medical teams should be aware of the management for such poisoning.

O-GlcNAc stimulation: A new metabolic approach to treat septic shock.

Septic shock is a systemic inflammation associated with cell metabolism disorders and cardiovascular dysfunction. Increases in O-GlcNAcylation have shown beneficial cardiovascular effects in acute pathologies. We used two different rat models to evaluate the beneficial effects of O-GlcNAc stimulation at the early phase of septic shock. Rats received lipopolysaccharide (LPS) to induce endotoxemic shock or saline (control) and fluid resuscitation (R) with or without O-GlcNAc stimulation (NButGT-10 mg/kg) 1 hour after shock induction. For the second model, rats received cecal ligature and puncture (CLP) surgery and fluid therapy with or without NButGT. Cardiovascular function was evaluated and heart and blood samples were collected and analysed. NButGT treatment efficiently increased total O-GlcNAc without modification of HBP enzyme expression.Treatment improved circulating parameters and cardiovascular function in both models, and restored SERCA2a expression levels. NButGT treatment also reduced animal mortality. In this study, we demonstrate that in septic shock O-GlcNAc stimulation improves global animal and cardiovascular function outcomes associated with a restoration of SERCA2a levels. This pre-clinical study opens avenues for a potential therapy of early-stage septic shock.