Max Andresen

Use of methylene blue in patients with refractory septic shock: Impact on hemodynamics and gas exchange

PURPOSE The purpose of this study was to assess the acute effects of methylene blue, an inhibitor of nitric oxide synthesis, on hemodynamics and gas exchange in patients with refractory septic shock in a prospective clinical trial at medical and surgical intensive care units in a tertiary university hospital. PATIENTS AND METHODS Prospective, sequential study of 10 consecutive patients admitted with severe septic shock of diverse causes and unable to achieve an adequate arterial pressure despite the use of at least two vasoactive drugs. Six of them also developed acute lung injury. All received 1 mg/kg intravenous bolus of methylene blue. Hemodynamic and respiratory parameters were measured at baseline and at 30, 60, 120, and 180 minutes after the bolus injection. RESULTS Systolic, diastolic, mean arterial blood pressure, and systemic vascular resistance increased significantly in all patients, whereas no significant changes were observed in cardiac output, oxygen consumption, or oxygen extraction ratio. Gas exchange remained unaffected in patients with acute lung injury. CONCLUSIONS Methylene blue had an acute vasopressor effect in patients with refractory septic shock, and it was not deleterious on respiratory function.

Lipoperoxidation and Protein Oxidative Damage Exhibit Different Kinetics During Septic Shock

Septic shock (SS)-related multiorgan dysfunction has been associated with oxidative damage, but little is known about the temporal damage profile and its relationship to severity. The present work investigated prospectively 21 SS patients. Blood samples were obtained at diagnosis, 24, 72 hours, day 7, and at 3 months. At admission, thiobarbituric acid reactive substances (TBARSs), plasma protein carbonyls, plasma protein methionine sulfoxide (MS), ferric/reducing antioxidant power (FRAP), total red blood cell glutathione (RBCG), uric acid (UA), and bilirrubin levels were increased (P < .05). Total radical—trapping antioxidant potential (TRAP) and vitamin-E were similar to controls, and vitamin-C was decreased (P < .05). During evolution, TBARS and RBCG increased (P < .001), vitamin-E levels remained stable, whereas plasma protein carbonyls and MS, TRAP, vitamin-C, reduced glutathione, and UA levels decreased (P < .006). After 3 months, plasma protein carbonyls and MS persisted elevated. More severe patients exhibited higher TBARS, TRAP, FRAP, vitamin-C, UA, and bilirrubin levels. Our results suggest early and persistent oxidative stress during septic shock and a correlation between increasing levels of lipoperoxidation and sepsis severity.

Sublingual microcirculatory changes during high-volume hemofiltration in hyperdynamic septic shock patients

IntroductionPrevious studies have suggested that high volume hemofiltration (HVHF) may contribute to revert hypotension in severe hyperdynamic septic shock patients. However, arterial pressure stabilization occurs due to an increase in systemic vascular resistance, which could eventually compromise microcirculatory blood flow and perfusion. The goal of this study was to determine if HVHF deteriorates sublingual microcirculation in severe hyperdynamic septic shock patients.MethodsThis was a prospective, non-randomized study at a 16-bed, medical-surgical intensive care unit of a university hospital. We included 12 severe hyperdynamic septic shock patients (norepinephrine requirements > 0.3 μg/kg/min and cardiac index > 3.0 L/min/m2) who underwent a 12-hour HVHF as a rescue therapy according to a predefined algorithm. Sublingual microcirculation (Microscan for NTSC, Microvision Medical), systemic hemodynamics and perfusion parameters were assessed at baseline, at 12 hours of HVHF, and 6 hours after stopping HVHF.ResultsMicrocirculatory flow index increased after 12 hours of HVHF and this increase persisted 6 hours after stopping HVHF. A similar trend was observed for the proportion of perfused microvessels. The increase in microcirculatory blood flow was inversely correlated with baseline levels. There was no significant change in microvascular density or heterogeneity during or after HVHF. Mean arterial pressure and systemic vascular resistance increased while lactate levels decreased after the 12-hour HVHF.ConclusionsThe use of HVHF as a rescue therapy in patients with severe hyperdynamic septic shock does not deteriorate sublingual microcirculatory blood flow despite the increase in systemic vascular resistance.

Características de los pacientes que reciben ventilación mecánica en unidades de cuidados intensivos: primer estudio multicéntrico chileno

Prospective cohort of consecutive adult patients admitted to 19 intensive care units(ICU) from 9 Chilean cities who received MV for more than 12 hours between September 1st, 2003,and September 28th, 2003. Demographic data, severity of illness, reason for the initiation of MV,ventilation modes and settings as well as weaning strategies were registered at the initiation and then,daily throughout the course of MV for up to 28 days. ICU and hospital mortality were recorded.

The implementation of an analgesia-based sedation protocol reduced deep sedation and proved to be safe and feasible in patients on mechanical ventilation

Introduction Deep sedation in critically ill patients is associated with a longer duration of mechanical ventilation and a prolonged length of stay in the intensive care unit. Several protocols have been used to improve these outcomes. We implement and evaluate an analgesia-based, goal-directed, nurse-driven sedation protocol used to treat critically ill patients who receive mechanical ventilation. Methods We performed a prospective, two-phase (before-after), non-randomized multicenter study that involved 13 intensive care units in Chile. After an observational phase (observational group, n=155), we designed, implemented and evaluated an analgesia-based, goal-directed, nurse-driven sedation protocol (intervention group, n=132) to treat patients who required mechanical ventilation for more than 48 hours. The primary outcome was to achieve ventilator-free days by day 28. Results The proportion of patients in deep sedation or in a coma decreased from 55.2% to 44.0% in the interventional group. Agitation did not change between the periods and remained approximately 7%. Ventilator-free days to day 28, length of stay in the intensive care unit and mortality were similar in both groups. At one year, post-traumatic stress disorder symptoms in survivors were similar in both groups. Conclusions We designed and implemented an analgesia-based, goal-directed, nurse-driven sedation protocol in Chile. Although there was no improvement in major outcomes, we observed that the present protocol was safe and feasible and that it resulted in decreased periods of deep sedation without increasing agitation.

Uso de inmunoglobulina humana endovenosa en pacientes con necrolisis epidérmica tóxica y síndrome de sobreposición Stevens Johnson necrolisis tóxica epidérmica

BACKGROUND Toxic epidemial necrolysis (TEN) is an acute adverse drug reaction, that has an unpredictableprogression and a 30% mortality. The incidence of TEN in the general population is approximately 0.4 to 1.2 cases/million/year. It is characterized pathologically by keratinocyte apoptosis which leads to epidemial detachment. Keratinocyte apoptosis is triggered by activation of the Fas-FasL, pathway and could be prevented by the use of intravenous immunoglobulin (IVIG). AIM To report the experience with the use of IVIG in TEN. MATERIAL AND METHODS Retrospective study of 15 patients with a diagnosis of Stevens-Johnson/TEN overlap (SJS/TEN) or TEN, that received a total dose of 23 +/- 0.6 mg/kg ofIVIG over aperiod of 3 to 4 days. The infusión was initiated during thefirst 24 hours after diagnosis and was associated with standard care for burn victims. Steroids were avoided if the patient was not in chronic steroidal therapy. RESULTS Allpatients responded to IVIG in a lapse of 46.4 +/- 14.2 hours from the beginning of infusión. Eighty percent of patients survived, but one developed acute renal failure due to IVIG, and another became blind due to corneal opacities, a complication of TEN. Those who survived were discharged after a lapse of 19-8 +/- 6.6 days from the beginning ofthe disease. CONCLUSIONS Despite the lack of blind, multicentric and randomized triáis, we agree with some international studies that TVIG is beneficial as a treatment for SSJ/NETand TEN .

Population pharmacokinetics and dose simulation of vancomycin in critically ill patients during high-volume haemofiltration.

This study aimed to describe the population pharmacokinetics of vancomycin in critically ill patients with refractory septic shock undergoing continuous venovenous high-volume haemofiltration (HVHF) and to define appropriate dosing for these patients. This was a prospective pharmacokinetic study in the ICU of a university hospital. Eight blood samples were taken over one vancomycin dosing interval. Samples were analysed by a validated liquid chromatography-tandem mass spectrometry assay. Non-linear mixed-effects modelling was used to describe the population pharmacokinetics. Dosing simulations were used to define therapeutic vancomycin doses for different HVHF settings. Nine patients were included (five male). The mean weight and SOFA score were 70 kg and 11, respectively. Mean HVHF settings were: blood flow rate, 240 mL/min; and haemofiltration exchange rate, 100 mL/kg/h. A linear two-compartment model with zero-order input adequately described the data. Mean parameter estimates were: clearance, 2.9 L/h; volume of distribution of central compartment (V(1)), 11.8L; volume of distribution of peripheral compartment (V(2)), 18.0 L; and intercompartmental clearance, 9.3 L/h. HVHF intensity was strongly associated with vancomycin clearance (P < 0.05) and was a covariate in the final model. Simulations indicate that after a loading dose, vancomycin doses required for different HVHF intensities would be 750 mg every 12h (q12h) for 69 mL/kg/h, 1000 mg q12h for 100 mL/kg/h and 1500 mg q12h for 123 mL/kg/h. Continuous infusion would also be a valuable administration strategy. In conclusion, variable and much higher than standard vancomycin doses are required to achieve therapeutic concentrations during different HVHF settings.

Fisiopatología de la insuficiencia renal aguda durante la sepsis

Acute renal failure (ARF) is an independent risk factor associated with increased mortality during sepsis. Recent consensus definitions have allowed the standardization of research on the subject. The understanding of the physiopathology of ARF during sepsis is limited by the scarcity of histological studies and the inability to measure renal microcirculatory flows. Historically, ARF during sepsis has been considered to be a consequence of diminished renal blood flow (RBF). Indeed, in early stages of sepsis or in sepsis associated to cardiogenic shock, RBF may decrease. However, recent studies have shown that in resuscitated sepsis, in which cardiac output is characteristically normal or even elevated and there is systemic vasodilatation, RBF is normal or even increased, with no associated histological evidence of significant tubular necrosis. Thus, other factors may participate in the genesis of ARF in sepsis. These include apoptosis, glomerular and medullary microcirculatory disorders, cell changes in response to the pro-inflammatory cascade characteristic of sepsis, oxidative stress, mitochondrial dysfunction and damage induced by mechanical ventilation, among others. Sepsis associated ARF treatment is supportive. In general, renal replacement therapies can be grouped as intermittent or continuous, and as those whose primary objective is the replacement of impaired renal function, versus those whose main objective is to secure hemodynamic stability through the clearing of pro-inflammatory mediators.

Características e impacto de la sedación, la analgesia y el bloqueo neuromuscular en los pacientes críticos que recibieron ventilación mecánica prolongada

AIM To describe use of sedatives, analgesics, and neuromuscular blockers (NMB) in patients undergoing long-term mechanical ventilation and to assess factors associated with their use and their association with mortality at 28 days. DESIGN Prospective observational multicenter cohort study. SETTING Thirteen intensive care units (ICU) in Chile. PATIENTS Patients undergoing mechanical ventilation for more than 48h. We excluded patients with neurological disorders, cirrhosis of the liver, chronic renal failure, suspected drug addiction, and early no resuscitation orders. INTERVENTION None. MAIN MEASUREMENTS Proportion of use and dosage of sedatives, analgesics, and NMB. Level of sedation observed (SAS). Variables associated with the Sedation Agitation Scale (SAS), use of sedatives, analgesics, and NMB. Multivariate logistic regression of variables associated to mortality at 28 days. RESULTS A total of 155 patients participated (60+/-18 years, 57% male, SOFA 7 [6-10], APACHE II 18 [15-22], 63% with sepsis, and 47% with acute lung injury/adult respiratory distress syndrome. The drugs most frequently used were midazolam (85%, 4 [1.9-6.8]mg/hr) and fentanyl (81%, 76 [39-140]microg/hr). NMB were administered at least 1 day in 30% of patients. SAS score was 1 or 2 in 55% of patients. There was an association between NMB use and mortality at 28 days, but it was not consistent in all the models of NMB evaluated. CONCLUSIONS Sedatives were frequently employed and deep sedation was common. Midazolam and fentanyl were the most frequently administered drugs. The use of NMB might be independently associated to greater mortality.

Consideraciones farmacocinéticas en el paciente crítico

Critically ill patients in Intensive Care Units (ICUs) are exposed to multiple procedures and usually require complex treatment regimens. Many of them suffer from comorbidities and different complications such as organ failure, drug-drug interactions, and unusual therapeutic interventions that can produce significant pathophysiologic changes. For that reason, pharmacokinetics for several substances is different to what is described for healthy patients, complicating drug selection and drug dosage to achieve appropriate effects. Low doses may determine a reduction of drug effectiveness and overdoses leading to toxicity. The aim of this paper is to review the pharmacokinetic considerations that must be considered when treating acute ICU patientsCritically ill patients in Intensive Care Units (ICUs) are exposed to multiple procedures and usually require complex treatment regimens. Many of them suffer from comorbidities and different complications such as organ failure, drug-drug interactions, and unusual therapeutic interventions that can produce significant pathophysiologic changes. For that reason, pharmacokinetics for several substances is different to what is described for healthy patients, complicating drug selection and drug dosage to achieve appropriate effects. Low doses may determine a reduction of drug effectiveness and overdoses leading to toxicity. The aim of this paper is to review the pharmacokinetic considerations that must be considered when treating acute ICU patients.