Norepinephrine Requirements Research Articles

Adjuvant hemoadsorption therapy in patients with severe COVID-19 and related organ failure requiring CRRT or ECMO therapy: A case series.

Severe cases of the COVID-19 are often associated with the development of a fulminant sepsis-like state with a concomitant cytokine release syndrome. Recently, immunomodulating approaches to treat such a hyperinflammation have come into focus, including the use of new extracorporeal organ support therapies such as CytoSorb hemoadsorption designed to remove cytokines and other circulating mediators from blood. Thirteen critically ill COVID-19 patients with ARDS who received either ECMO therapy and/or CRRT with concomitant multiple organ failure were included. Hemoadsorption therapy was initiated once the patient had established-or was at high risk of developing-a hyperinflammatory state with marked hemodynamic instability or progressive lung failure. Levels of inflammatory markers, vasopressor requirements, oxygenation, and ventilation parameters were measured, as well as clinically relevant outcome measures. Combined therapy was associated with a significant reduction in inflammatory mediators, hemodynamic stabilization with a concomitant decrease in requirements for vasoactive substances, and a pronounced improvement in lung function and the need for ventilatory support. Treatment appeared safe and well-tolerated. In this case series of SARS-CoV-2 infected patients admitted to the intensive care unit with ARDS, we report effective interleukin (IL)-6 removal, reduced norepinephrine requirement, and improved lung function while receiving adjuvant, extracorporeal hemoadsorption therapy in the context of a multimodal treatment approach. The presented protocol for CytoSorb initiation may be a good foundation for the development of further prospective studies in the field and may eventually also be applied to other forms of hyperinflammatory ARDS.

Blood purification with CytoSorb in critically ill COVID-19 patients: A case series of 26 patients.

Severe forms of the coronavirus disease 2019 (COVID‐19) can progress to sepsis‐like complications accompanied by “cytokine storm” for which the most effective treatment has not yet been established. Our study describes the results of CytoSorb hemoadsorption in COVID‐19 patients treated on the intensive care unit (ICU). In this retrospective study, 26 patients with COVID‐19 and acute respiratory distress syndrome (ARDS) were treated with hemoadsorption therapy. Pre‐, and post‐treatment values (clinical and laboratory) were compared. Data are expressed as mean (confidence intervals, CI), or median [interquartile ranges, IQR], as appropriate. Patients received 2 hemoadsorption treatments. This resulted in a significant decrease in norepinephrine requirements, and inflammatory marker plasma concentrations (procalcitonin, C‐reactive protein, ferritin) when comparing pre versus post treatment levels. The PaO2/FiO2 and overall organ function (ie, Sequential Organ Failure Assessment—SOFA score) also improved significantly. Patients stayed on the ICU for 9 days and 21 of them survived. To the best of our knowledge, this is one of the largest case series to date reporting early experiences on extracorporeal hemoadsorption therapy in SARS‐CoV‐2 positive patients with hyperinflammation and moderate ARDS. Treatment proved to be effective, technically feasible and well‐tolerated.

The Potential Role of Extracorporeal Cytokine Removal in Hemodynamic Stabilization in Hyperinflammatory Shock.

Hemodynamic instability due to dysregulated host response is a life-threatening condition requiring vasopressors and vital organ support. Hemoadsorption with Cytosorb has proven to be effective in reducing cytokines and possibly in attenuating the devastating effects of the cytokine storm originating from the immune over-response to the initial insult. We reviewed the PubMed database to assess evidence of the impact of Cytosorb on norepinephrine needs in the critically ill. We further analyzed those studies including data on control cohorts in a comparative pooled analysis, defining a treatment effect as the standardized mean differences in relative reductions in vasopressor dosage at 24 h. The literature search returned 33 eligible studies. We found evidence of a significant reduction in norepinephrine requirement after treatment: median before, 0.55 (IQR: 0.39–0.90); after, 0.09 (0.00–0.25) μg/kg/min, p < 0.001. The pooled effect size at 24 h was large, though characterized by high heterogeneity. In light of the importance of a quick resolution of hemodynamic instability in the critically ill, further research is encouraged to enrich knowledge on the potentials of the therapy.

Effects of Sodium Thiosulfate During Resuscitation From Trauma-and-Hemorrhage in Cystathionine Gamma Lyase (CSE) Knockout Mice.

Sodium thiosulfate (Na2S2O3) is a clinically established drug with antioxidant and sulphide-releasing properties. Na2S2O3 mediated neuro- and cardioprotective effects in ischemia/reperfusion models and anti-inflammatory effects in LPS-induced acute lung injury. Moreover, Na2S2O3 improved lung function during resuscitation from hemorrhagic shock in swine with pre-existing atherosclerosis, characterized by decreased expression of cystathionine γ-lyase (CSE), a major source of hydrogen sulfide (H2S) synthesis in the vasculature. Based on these findings, we investigated the effects of Na2S2O3 administration during resuscitation from trauma-and-hemorrhage in mice under conditions of whole body CSE deficit. After blast wave-induced blunt chest trauma and surgical instrumentation, CSE knockout (CSE-/-) mice underwent 1 h of hemorrhagic shock (MAP 35 ± 5 mm Hg). At the beginning of resuscitation comprising retransfusion, norepinephrine support and lung-protective mechanical ventilation, animals received either i.v. Na2S2O3 (0.45 mg g-1, n = 12) or vehicle (saline, n = 13). Hemodynamics, acid-base status, metabolism using stable isotopes, and visceral organ function were assessed. Blood and organs were collected for analysis of cytokines, mitochondrial respiratory capacity, and immunoblotting. Na2S2O3 treatment improved arterial paO2 (P = 0.03) coinciding with higher lung tissue glucocorticoid receptor expression. Norepinephrine requirements were lower in the Na2S2O3 group (P < 0.05), which was associated with lower endogenous glucose production and higher urine output. Na2S2O3 significantly increased renal tissue IκBα and heme oxygenase-1 expression, whereas it lowered kidney IL-6 and MCP-1 levels. Na2S2O3 exerted beneficial effects during resuscitation of murine trauma-and-hemorrhage in CSE-/- mice, confirming and extending the previously described organ-protective and anti-inflammatory properties of Na2S2O3. The findings make Na2S2O3 a potentially promising therapeutic option in the context of impaired CSE activity and/or reduced endogenous H2S availability.

Inhaled nitric oxide improves pulmonary hypertension and organ functions after adult heart valve surgeries.

Pulmonary hypertension during cardiac surgery is associated with increased morbidity and mortality. Inhaled nitric oxide serves as a selective pulmonary vasodilator and has other potential extrapulmonary protective roles. Its effects on pulmonary hypertension and organ functions after adult valve surgeries were evaluated. From April 2017 to March 2000, 30 patients received inhaled nitric oxide therapy for pulmonary hypertension during weaning from cardiopulmonary bypass in valvular surgery (iNO group). The group was compared with a control group of 65 patients who developed pulmonary hypertension during weaning from cardiopulmonary bypass in valvular surgery and received conventional therapy from April 2014 to March 2017. Intraoperative hemodynamic changes and postoperative Sequential Organ Failure Assessment (SOFA) score were evaluated. The inhalation of nitric oxide lowered the pulmonary-to-systemic pressure ratio (Pp/Ps) (p < 0.0001) in the iNO group, and this ratio after the inhalation was significantly lower than that in the control group (p = 0.015). Moreover, norepinephrine requirement was lower in the iNO group than in the control group (p = 0.0060). The SOFA total scores, respiratory scores, coagulation scores, and the increase of renal scores within postoperative 2 days were lower in the iNO group than in the control group (p < 0.0001, p = 0.0002, p = 0.0013, and p = 0.037). Inhaled nitric oxide therapy ameliorated pulmonary hypertension and improved postoperative respiratory, coagulation, and renal functions in adult valve surgeries.

Early ICU-acquired hypernatraemia is associated with injury severity and preceded by reduced renal sodium and chloride excretion in polytrauma patients.

To further elucidate the origin of early ICU-acquired hypernatraemia. In this retrospective single-centre study, polytrauma patients requiring ICU treatment were analysed. Forty-eight (47.5%) of 101 included polytrauma patients developed hypernatraemia within the first 7 days on ICU. They were more severely ill as described by higher SAPS III, ISS, daily SOFA scores and initial norepinephrine requirements as well as longer requirements of mechanical ventilation and ICU treatment in general. The development of hypernatraemia was neither attributable to fluid- or sodium-balances nor renal impairment. Although lower in the hypernatraemic group from day 4 onwards, median creatinine clearances were sufficiently high throughout the observation period. However, in the hypernatraemic group, urine sodium and chloride concentrations prior to the evolvement of hypernatraemia (56 (27-87) mmol/l and 39 (23-77) mmol/l) were significantly decreased when compared to i) the time after developing hypernatraemia (94 (58-134) mmol/l and 78 (36-115) mmol/l; p < 0.001) and ii) the non-hypernatraemic group in general (101 (66-143) mmol/l and 75 (47-109) mmol/l; p < 0.001). Early ICU-acquired hypernatraemia is associated with injury severity and preceded by reduced renal sodium and chloride excretion in polytrauma patients.

Left Ventricular Decompression by Transaortic Catheter Venting in Extracorporeal Membrane Oxygenation.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been widely applied to patients with cardiogenic shock. Left ventricle (LV) decompression is important when LV distension develops with pulmonary edema. The purpose of this study was to present the results of transaortic catheter venting (TACV) performed during VA-ECMO. We retrospectively reviewed the medical records of 18 patients who underwent both VA-ECMO and TACV between January 2017 and December 2019. Venoarterial extracorporeal membrane oxygenation was applied uneventfully. Lactate level and norepinephrine requirement for patients of weaning success were lower than those of patients of weaning failure after the application of TACV (p = 0.032 and p = 0.015, respectively). The successful weaning rate of ECMO was 77.8% (15/18) and survival rate was 50% (9/18). Transaortic catheter venting may be an easy, safe, and effective technique for LV decompression in patients with VA-ECMO for cardiogenic shock. Also, this technique may be helpful as an alternative or bridge method.

Is the autonomic nervous system explaining norepinephrine requirements decrease in septic shock patients following administration of alpha-2 agonists?

Is the autonomic nervous system explaining norepinephrine requirements decrease in septic shock patients following administration of alpha-2 agonists?

High Oxygen is Likely to be Beneficial on Cardiac Contractility after Normothermic Regional Perfusion after Circulatory Death in a Porcine Model

<h3>Purpose</h3> The impact of high versus low oxygenation during normothermic regional perfusion (NRP) after anoxic circulatory death on donor heart contractility in a porcine model. <h3>Methods</h3> The animals were anaesthetized, pressure-volume catheters were placed in both ventricles and a pulmonary artery catheter was inserted percutaneously. Through a midline sternotomy, the heparinized animals were cannulated for extracorporeal circulation. Baseline data were obtained. Mechanical ventilation was withdrawn. After 15 minutes of warm ischemia, the aortic arch vessels and infrarenal aorta were clamped before NRP was commenced using a standard heart-lung machine. The animals were randomized to receive either FiO2 of 1.0 (HOX) or 0.21 (LOX) with a gradual increase to 0.40 during NRP. The NRP protocol includes early volume loading of the right ventricle and gradual wean over 35 minutes. Dobutamine and norepinephrine infusions were started during NRP for circulatory support. The animals were observed for 180 minutes after weaning from NRP. <h3>Results</h3> 15 of 19 animals were successfully weaned from NRP; 8/9 in the HOX and 7/10 in the LOX group, (p = 0.58). All weaned animals displayed acceptable cardiac function during the observation period and sustained a mean arterial pressure >60 mmHg with low filling pressures and cardiac index >2.5 L/min/m². The preload independent end-systolic pressure volume relationship as an index of contractility was preserved in both groups. The HOX RV contractility was higher than the LOX group (p=0.035); and not significantly in the LV (p=0.37) (Fig. 1). Biochemestry showed lower lactate levels in the HOX group. There was no difference in norepinephrine requirement between groups. <h3>Conclusion</h3> There were minimal haemodynamic and biochemical differences between the groups as all weaned animals demonstrated acceptable cardiac function. The high oxygenation group showed marginally better cardiac performance and lower lactate concentrations.

Different mechanisms of oxygenator failure and high plasma von Willebrand factor antigen influence success and survival of venovenous extracorporeal membrane oxygenation.

ObjectiveFailure of membrane oxygenator (MO) function of venovenous extracorporeal membrane oxygenators (VV ECMO) remains problematic. The development of device-induced coagulation disorder (COD) or worsened gas transfer (WGT) necessitates a system exchange. The aim was to correlate von Willebrand factor antigen (vWF:Ag) with the predisposition to MO failure and mortality.MethodsLaboratory parameters (inflammation, coagulation) and ECMO-related data from 31 VV ECMO patients were analyzed before and after the first MO exchange. Study groups were identified according to the exchange reasons (COD, WGT) and the extent of vWF:Ag (low, ≤425%; high, >425%).ResultsvWF:Ag remained unchanged after system exchange. High vWF:Ag was associated with systemic endothelial activation of older and obese patients with elevated SOFA score, increased norepinephrine and higher requirement of continuous renal replacement therapy without an effect on MO runtime and mortality. Including the mechanism of MO failure (COD, WGT), various patient group emerged. COD/low vWF:Ag summarized younger and less critically ill patients that benefit mainly from ECMO by a significant improvement of their inflammatory and coagulation status (CRP, D-dimers, fibrinogen) and highest survival rate (91%). Instead, WGT/high vWF:Ag presented older and more obese patients with a two-digit SOFA score, highest norepinephrine, and aggravated gas transfer. They benefited temporarily from system exchange but with worst survival (33%).ConclusionsvWF:Ag levels alone cannot predict early MO failure and outcome in VV ECMO patients. Probably, the mechanism of clotting disorder in combination with the vWF:Ag level seems to be essential for clot formation within the MO. In addition, vWF:Ag levels allows the identification different patient populations In particular, WGT/high vWF:Ag represented a critically ill population with higher ECMO-associated mortality.

Hemodynamic and anti-inflammatory effects of early esmolol use in hyperkinetic septic shock: a pilot study

BackgroundSeveral studies have shown that heart rate control with selective beta-1 blockers in septic shock is safe. In these trials, esmolol was administered 24 h after onset of septic shock in patients who remained tachycardic. While an earlier use of beta-blockers might be beneficial, such use remains challenging due to the difficulty in distinguishing between compensatory and non-compensatory tachycardia. Therefore, the Esmosepsis study was designed to study the effects of esmolol aimed at reducing the heart rate by 20% after the initial resuscitation process in hyperkinetic septic shock patients on (1) cardiac index and (2) systemic and regional hemodynamics as well as inflammatory patterns.MethodsNine consecutive stabilized tachycardic hyperkinetic septic shock patients treated with norepinephrine for a minimum of 6 h were included. Esmolol was infused during 6 h in order to decrease the heart rate by 20%. The following data were recorded at hours H0 (before esmolol administration), H1–H6 (esmolol administration) and 1 h after esmolol cessation (H7): systolic arterial pressure, diastolic arterial pressure, mean arterial pressure, central venous pressure, heart rate, PICCO transpulmonary thermodilution, sublingual and musculo-cutaneous microcirculation, indocyanine green clearance and echocardiographic parameters, diuresis, lactate, and arterial and venous blood gases.ResultsEsmolol was infused 9 (6.4–11.6) hours after norepinephrine introduction. Esmolol was ceased early in 3 out of 9 patients due to a marked increase in norepinephrine requirement associated with a picture of persistent cardiac failure at the lowest esmolol dose. For the global group, during esmolol infusion, norepinephrine infusion increased from 0.49 (0.34–0.83) to 0.78 (0.3–1.11) µg/min/kg. The use of esmolol was associated with a significant decrease in heart rate from 115 (110–125) to 100 (92–103) beats/min and a decrease in cardiac index from 4.2 (3.1–4.4) to 2.9 (2.5–3.7) l/min/m−2. Indexed stroke volume remained unchanged. Cardiac function index and global ejection fraction also markedly decreased. Using echocardiography, systolic, diastolic as well as left and right ventricular function parameters worsened. After esmolol cessation, all parameters returned to baseline values. Lactate and microcirculatory parameters did not change while the majority of pro-inflammatory proteins decreased in all patients.ConclusionIn the very early phase of septic shock, heart rate reduction using fast esmolol titration is associated with an increased risk of hypotension and decreased cardiac index despite maintained adequate tissue perfusion (NCT02068287).

Use of Sorbent Based on Hypercrosslinked Styrene-Divinylbenzene Copolymer With Immobilized LPS-Selective Ligand In Hemoperfusion For Treatment of Patients With Septic Shock

Aim of the study : to evaluate safety and feasibility of clinical use of an extracorporeal blood adsorber based on a hypercrosslinked styrene-divinylbenzene copolymer with immobilized lipopolysaccharide (LPS)-selective ligand designed to remove endotoxins from the bloodstream to treat patients with septic shock. Materials and methods . Nine patients (mean age 58 years, 5 men and 4 women, initial median APACHE II score 28 points, SOFA score 10 points) with confirmed Gram-negative bacterial infection and septic shock (SEPSIS-3, 2016) underwent LPS-selective hemoperfusion using an extracorporeal blood adsorber based on a hypercrosslinked styrene divinylbenzene copolymer with immobilized LPS-selective ligand for 6 hours, followed by prolonged veno-venous hemodiafiltration. Before the hemoperfusion (day 0), immediately after it, a day after its end (day 1) and once daily for the next 4 days we assessed the hemodynamic parameters, oxygenation, organ failure signs, white blood cell count, procalcitonin, C-reactive protein, clinical chemistry parameters. Results. Hemoperfusion resulted in a rapid decrease in the endotoxin activity (EAA test), more than twofold decrease in plasma level of interleukin-1 (immunoenzyme test). At the end of the procedure, the plasma lactate level decreased to normal values by day 3, pH values restored to normal within 1-2 days. The noradrenaline requirement rapidly decreased and completely resolved within 1-3 days, which corresponded to the restoration of mean blood pressure values. The values of the PaO2/FiO2 oxygenation index increased significantly after 24 hours, and the median values of 300 were maintained during all subsequent days of observation. During the first day, hemoperfudion caused a rapid decline in APACHE II and SOFA scores, while acute renal failure (estimated by urea and creatinine levels) resolved gradually by day 5. The hemoperfusion did not affect the unchanged coagulation parameters (prothrombin, fibrinogen, INR). During the first day after the procedure, we observed a short-term 1.5-fold decrease in platelet count with subsequent recovery by days 2-3 in most patients. Two patients, both differing from the rest of the patients prior to treatment in the highest values of APACHE II score (above 30), APTT (above 40) and endotoxin activity in EAA test (above 0.9), died on the 4th and 8th days of treatment. The rest of the patients survived, with clinical improvement in all parameters. Conclusion . The results of extracorporeal blood purification using Efferon LPS extracorporeal blood adsorber indicate a high therapeutic potential of the method and suggest the need for extended clinical trials to assess its clinical efficacy in ICU to reduce the high mortality in patients with septic shock.

UNCOMMON AMONGST COMMON: ANGIOTENSIN II-INDUCED PERIPHERAL ISCHEMIA IN REFRACTORY SEPTIC SHOCK

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Angiotensin (AT) II, a naturally occurring hormone, modulates blood pressure through direct vasoconstriction of the circulatory system and through stimulation of various catecholamines and vasopressin. Derived from the hydrolysis of AT I via the AT-converting enzyme (ACE) in the pulmonary & renal endothelium, AT II has been studied for cases of vasodilatory shock since the 1930’. Most recently, the ATHOS-3 trial demonstrated AT II’s utility as a rescue vasopressor agent, highlighting its catecholamine-sparing effects. CASE PRESENTATION: 34-year-old African American male presented with 3-day history of dyspnea, productive cough and an episode of hemoptysis. Upon presentation, he was febrile, tachycardic, hypotensive and hypoxic prompting endotracheal intubation and vasopressor support. Laboratory studies were significant for leukocytosis with bandemia, lactic acidosis, acute kidney injury, transaminitis & positive for influenza A. Despite aggressive critical care management with maximum ventilator requirements, broad-spectrum antibiotics, renal replacement therapy & proning, his overall condition continued to worsen. AT II was initiated on Day 2 of ICU admission for refractory hypotension secondary to septic shock. Approximately 48-72 hours after the initiation of AT II, he developed skin discoloration and blistering in all extremities secondary to both arterial and venous thromboemboli despite prophylaxis. The lesions ultimately progressed leading to gangrenous necrosis extending proximally to the torso. Unfortunately, on day 7 of ICU admission, patient suffered a cardiac arrest and expired despite ACLS efforts. DISCUSSION: In our patient, we exhibited similar results to those described in the ATHOS-3 trials. Administration of the AT II resulted in an overall improvement in the patient’s mean arterial pressure, systemic vascular resistance and reduced norepinephrine requirements. We also observed a concomitant improvement in serum lactate, indicating improvement in overall organ perfusion. There are no absolute contraindications to AT II administration, but ATHOS-3 did report an increased incidence of both venous and arterial thromboembolic events in patients who received AT II. Although AT II has been FDA approved for the management of refractory septic shock, more studies are necessary to define those populations most at risk of the adverse effects. CONCLUSIONS: AT II is an important vasopressor agent used in refractory shock; however, more studies are needed to understand the adverse effects in populations most at risk. Reference #1: National Center for Biotechnology Information. PubChem Database. Angiotensin II, CID=172198, https://pubchem.ncbi.nlm.nih.gov/compound/Angiotensin-II (accessed on Mar. 26, 2020) DISCLOSURES: No relevant relationships by Krupa Gandhi, source=Web Response No relevant relationships by Mohit Mody, source=Web Response

Evaluation of the Initiation Timing of Hydrocortisone in Adult Patients With Septic Shock.

Clinical studies evaluating the use of hydrocortisone in patients with septic shock are heterogeneous in design with conflicting results. The appropriate time in which to initiate hydrocortisone after shock onset is unknown. This study sought to compare clinical outcomes including vasopressor duration and mortality in patients with septic shock who received hydrocortisone based on timing of initiation after shock onset. Retrospective cohort study of patients between 2011 and 2017 admitted to 10 medical, surgical, and neurosciences intensive care units (ICUs) at a large, tertiary care academic medical center. Adult patients with vasopressor-dependent septic shock who received hydrocortisone were included. Patients were divided into five timing cohorts based on time after shock onset: 0-6, 6-12, 12-24, 24-48, or >48 h. The primary outcome was days alive and free from vasopressors. One thousand four hundred seventy patients were included: 567 (38.6%) received hydrocortisone between 0 and 6 h, 231 (15.7%) 6 and 12 h, 260 (17.7%) 12 and 24 h, 195 (13.3%) 24 and 48 h, and 217 (14.8%) >48 h after shock onset. Patients who received hydrocortisone earlier were sicker at baseline with higher APACHE III scores, lactate concentrations, and norepinephrine requirements. On univariate analysis, days alive and free from vasopressors did not significantly differ amongst the timing groups (median 3.3 days for 0-6 h; 1.9 for 6-12 h; 1.9 for 12-24 h; 0 for 24-48 h; 0 for >48 h; P = 0.39); similarly, ICU mortality did not differ. On multivariable linear regression, timing of hydrocortisone was independently associated with more days alive and free from vasopressors when comparing initiation within 0 to 6 h with >48 h (beta-coefficient 2.8 days [95% CI 0.8-4.7]), 6-12 h with >48 h (2.5 days [95% CI 0.2-4.7]), and 12-24 h with >48 h (2.3 days [95% CI 0.2-4.5]). On multivariable logistic regression, timing of hydrocortisone was associated with reduced ICU mortality when comparing receipt within 0 to 6 h of shock onset to >48 h after shock onset (OR 0.6, 95% CI 0.4-0.8). In patients in whom hydrocortisone is prescribed for vasopressor-dependent septic shock, timing is crucial and hydrocortisone should be started within the first 12 h after shock onset.

Methylene Blue Does Not Improve Vasoplegia After Left Ventricular Assist Device Implantation

Vasoplegia is a frequent complication of left ventricular assist device (LVAD) implantation. We investigated the effectiveness of methylene blue (MB) for vasoplegia in LVAD recipients. Twenty-seven patients received MB for vasoplegia after LVAD implantation and met study criteria between March 2015 and May 2018. Propensity score inverse probability weighting identified 41 controls who did not receive MB for post-LVAD vasoplegia. Clinical outcomes were compared between control and MB groups and between patients who received doses during (n= 15) and after surgery (n= 12). Hemodynamics and vasopressor requirements were analyzed using analysis of covariance. Median total MB dose was 1.9 mg/kg (interquartile range, 1.2-2.2 mg/kg). Methylene blue recipients experienced a transient initial decline in norepinephrine requirement from 141 ng/kg per min (95% confidence interval [CI], 81-201 ng/kg per min) to 117 ng/kg per min (95% CI, 58-176 ng/kg per min; P= .022) and a delayed decline in vasopressin from 4.8 U/h (95% CI, 3.8-5.8 U/h) to 4.0 U/h (95% CI, 2.8-5.1 U/h) (P= .004). In-hospital mortality, postoperative complications, and end-organ dysfunction did not differ from those of controls. There were no observed differences in mean arterial pressure, vasopressor requirements, or outcomes between patients who received doses during or after surgery. Weighted overall mortality in the entire study cohort was 8.8%. Although MB may affect vasopressor requirements, clinical outcomes in vasoplegia after LVAD implantation did not improve and were not affected by the timing of administration.

LEVOSIMENDAN AFTER CARDIAC SURGERY: A SINGLE-CENTER CASE SERIES

TYPE: Abstract Publication TOPIC: Critical Care PURPOSE: The purpose of this study is to describe the short-term effect of Levosimendan on hemodynamics and inotropic/vasopressor requirements after different types of cardiac surgery. METHODS: This retrospective review was conducted between April 2012 and November 2019 on patients recieving levosimendan after cardiac surgery. Exclusion criteria for analysis were heart transplantation, ECMO, assist devices and multiple levosimendan doses. Levosimendan was administered postoperatively as a continuous infusion, without a loading dose. Age, sex, mortality, dose and duration of levosimendan infusion, preoperative Euroscore II and need for renal replacement therapy (RRT) were collected from medical files. Mean arterial pressure (MAP), heart rate, lactate, dobutamine and noradrenaline requirements were collected before, at conclusion of, and 24 hours after levosimendan infusion. RESULTS: Data of 78 patients were retrieved: 49 (63%) of the patients were male and 29 (37%) were female. Age was 74 (±10) years. Euroscore II was 9.75 (±12.5). A total dose of 12.5 mg levosimendan was administered at 0.05-0.2 μg/kg/min. Duration of infusion was 34.4 (±15.4) hours. Heart rate, MAP, lactate and dobutamine/noradrenaline requirements are shown in Table 1. Fourteen patients (18%) had a intra-aortic balloon pump at the start of levosimendan infusion. Renal replacement therapy was needed in 26 patients (33.3%). ICU and 28-day mortality were 7.6% (n=6) and 2.5% (n=2), respectively. CONCLUSIONS: In patients with LCOS after cardiac surgery levosimendan infusion, without a loading dose, reduced the need for dobutamine and noradrenaline up to 24 hours postinfusion, without inducing hypotension. CLINICAL IMPLICATIONS: Levosimendan in LCOS after cardiac surgery is safe and reduces the need of catecholamines. DISCLOSURE: No significant relationships. KEYWORD: Levosimendan

Are other effects of dexmedetomidine playing a role in explaining norepinephrine requirements decrease in septic shock patients?

article: Are other effects of dexmedetomidine playing a role in explaining norepinephrine requirements decrease in septic shock patients? - Minerva Anestesiologica 2021 January;87(1):107-8 - Minerva Medica - Journals

Safety and Effectiveness of Sedation With Adjunctive Ketamine Versus Nonketamine Sedation in the Medical Intensive Care Unit

Background: Ketamine, an N-methyl-d-aspartate receptor antagonist with sedative and analgesic properties, is becoming more popular as an adjunctive sedative in the critically ill patients. Methods: We conducted a single center, retrospective cohort study of patients admitted to the medical intensive care unit (MICU) between 2013 and 2018. Patients who received continuous infusion ketamine or nonketamine sedatives (NKS) including dexmedetomidine, fentanyl, midazolam, or propofol were identified. The primary outcome was percentage of Richmond Agitation-Sedation Scale (RASS) scores at goal in patients receiving ketamine as adjunct to NKS compared to those on NKS alone. Results: A total of 172 patients were included (n = 86 ketamine, n = 86 NKS). Baseline characteristics were similar with the exception of antipsychotic use, which was higher in the ketamine group (P = .008). Percentage of RASS scores at goal was not different between groups (78.7% vs 81.4%, P = .29). Fewer patients in the ketamine group received continuous infusion fentanyl (76.7% vs 94.2%, P = .002). Patients on adjunctive ketamine required fewer days of intermittent benzodiazepines (0 [0-1] vs 1 [1-2], P < .0001). Patients receiving ketamine required less norepinephrine, receiving a median of 6.32 mg (2.4-20) versus 11.7 mg (5.2-45.2; P = .03). There was no difference in receipt of new antipsychotics or occurrence of arrhythmias. Conclusion: Addition of ketamine did not increase the percentage of RASS scores at goal versus NKS but was well tolerated. Ketamine was associated with reductions in norepinephrine requirements, days of intermittent benzodiazepine administration, and number of patients receiving continuous infusion fentanyl. Continuous infusion ketamine appears safe and effective for sedation in the MICU.

Cardiovascular Safety of Clonidine and Dexmedetomidine in Critically Ill Patients after Cardiac Surgery.

Purpose The aim of this retrospective study was to assess the haemodynamic adverse effects of clonidine and dexmedetomidine in critically ill patients after cardiac surgery. Methods 2769 patients were screened during the 30-month study period. Heart rate (HR), mean arterial pressure (MAP), and norepinephrine requirements were assessed 3-hourly during the first 12 hours of the continuous drug infusion. Results are given as median (interquartile range) or numbers (percentages). Results Patients receiving clonidine (n = 193) were younger (66 (57–73) vs 70 (63–77) years, p=0.003) and had a lower SAPS II (35 (27–48) vs 41 (31–54), p=0.008) compared with patients receiving dexmedetomidine (n = 141). At the start of the drug infusion, HR (90 (75–100) vs 90 (80–105) bpm, p=0.028), MAP (70 (65–80) vs 70 (65–75) mmHg, p=0.093), and norepinephrine (0.05 (0.00–0.11) vs 0.12 (0.03–0.19) mcg/kg/min, p < 0.001) were recorded in patients with clonidine and dexmedetomidine. Bradycardia (HR < 60 bpm) developed in 7.8% with clonidine and 5.7% with dexmedetomidine (p=0.51). Between baseline and 12 hours, norepinephrine remained stable in the clonidine group (0.00 (−0.04–0.02) mcg/kg/min) and decreased in the dexmedetomidine group (−0.03 (−0.10–0.02) mcg/kg/min, p=0.007). Conclusions Dexmedetomidine and the low-cost drug clonidine can both be used safely in selected patients after cardiac surgery.

Vasopressine et analogues dans les états de choc

Le système vasopressinergique est l’un des systèmes activés en réponse à une baisse de la pression artérielle. La vasopressine, hormone de stress, entraîne après sa fixation sur les récepteurs V1a des cellules musculaires lisses vasculaires, une vasoconstriction.Au cours du choc septique, la mise en évidence de taux de vasopressine anormalement bas en regard de l’hypotension artérielle, et la capacité de correction de l’hypotension artérielle après administration de vasopressine, ont suscité un vif intérêt des cliniciens. Des analogues de synthèse, avec une plus forte affinité pour les récepteurs vasculaires de la vasopressine ont été développés : la terlipressine et la selepressine.Nous présentons dans cette revue les bénéfices et les risques inhérents à son administration au cours du choc septique et vasoplégique post-opératoire de chirurgie cardiaque. L’administration de vasopressine et ses agonistes permet de diminuer la quantité de noradrénaline administrée, et parmi les effets indésirables liés à son usage, la survenue d’ischémie digitale est la plus fréquente.Enfin, nous tenterons de préciser la place actuelle à proposer à ces molécules en fonction des données de la littérature disponibles, et les questions qui subsistent.