Dimitrios Velissaris

Acute Respiratory Distress Syndrome: Pathophysiology and Therapeutic Options

Acute Respiratory Distress Syndrome (ARDS) is a common entity in critical care. ARDS is associated with many diagnoses, including trauma and sepsis, can lead to multiple organ failure and has high mortality. The present article is a narrative review of the literature on ARDS, including ARDS pathophysiology and therapeutic options currently being evaluated or in use in clinical practice. The literature review covers relevant publications until January 2011. Recent developments in the therapeutic approach to ARDS include refinements of mechanical ventilatory support with emphasis on protective lung ventilation using low tidal volumes, increased PEEP with use of recruitment maneuvers to promote reopening of collapsed lung alveoli, prone position as rescue therapy for severe hypoxemia, and high frequency ventilation. Supportive measures in the management of ARDS include attention to fluid balance, restrictive transfusion strategies, and minimization of sedatives and neuromuscular blocking agents. Inhaled bronchodilators such as inhaled nitric oxide and prostaglandins confer short term improvement without proven effect on survival, but are currently used in many centers. Use of corticosteroids is also important, and appropriate timely use may reduce mortality. Finally, extra corporeal oxygenation methods are very useful as rescue therapy in patients with intractable hypoxemia, even though a survival benefit has not, to this date been demonstrated. Despite intense ongoing research on the pathophysiology and treatment of ARDS, mortality remains high. Many pharmacologic and supportive strategies have shown promising results, but data from large randomized clinical trials are needed to fully evaluate the true effectiveness of these therapies. Keywords ARDS; Pathophysiology; Treatment

Administration of tetrahydrobiopterin improves the microcirculation and outcome in an ovine model of septic shock.

Objective: Supplementation with tetrahydrobiopterin, a nitric oxide synthase cofactor, may reduce microvascular endothelial dysfunction in severe sepsis. We studied whether tetrahydrobiopterin administration exerts beneficial effects in an ovine septic shock model. Design: Randomized animal study. Setting: University hospital animal research laboratory. Subjects: Fourteen adult female sheep. Interventions: Fecal peritonitis was induced, and the sheep were randomized to receive tetrahydrobiopterin (n = 7), given intravenously as 20mg/kg boluses at 4 and 12 hrs after sepsis induction, or placebo (n = 7). All animals were fluid resuscitated. The experiment was continued until death or for a maximum of 30 hrs. Measurements and Main Results: In addition to standard hemodynamic assessment, the sublingual microcirculation was evaluated using sidestream dark-field videomicroscopy. The first bolus of tetrahydrobiopterin blunted the increase in heart rate and cardiac index seen in the control group without affecting mean arterial pressure, and the second bolus of tetrahydrobiopterin prevented the decreases in cardiac index and mean arterial pressure. The reduction in mixed venous blood oxygen saturation and the increase in blood lactate seen in the control group were also delayed. Tetrahydrobiopterin significantly attenuated the deterioration in perfused small vessel proportion and density, microvascular flow index, and the increase in microvascular heterogeneity observed in the control group. Tetrahydrobiopterin was associated with better preserved lung compliance and PaO2/FIO2 ratio, which were associated with a lower lung wet/dry weight ratio at the end of the study. Median survival time was significantly prolonged in the tetrahydrobiopterin group (25.0 vs. 17.8 hrs, p < .01). Conclusion: In this clinically relevant model of sepsis, tetrahydrobiopterin supplementation attenuated the impairment in sublingual microvascular perfusion and permeability, which was accompanied by better preserved gas exchange, renal flow and urine output, and prolonged survival.

Impact of infection on the prognosis of critically ill cirrhotic patients: results from a large worldwide study

Infections are a leading cause of death in patients with advanced cirrhosis, but there are relatively few data on the epidemiology of infection in intensive care unit (ICU) patients with cirrhosis.

High mixed venous oxygen saturation levels do not exclude fluid responsiveness in critically ill septic patients

IntroductionThe aim of this study was to determine whether the degree of fluid responsiveness in critically ill septic patients is related to baseline mixed venous oxygen saturation (SvO2) levels. We also sought to define whether fluid responsiveness would be less likely in the presence of a high SvO2 (>70%).MethodsThis observational study was conducted in a 32-bed university hospital medicosurgical ICU. The hemodynamic response to a fluid challenge was evaluated in 65 critically ill patients with severe sepsis. Patients were divided into two groups (responders and nonresponders) according to their cardiac index (CI) response to the challenge (>10% or <10%).ResultsOf the 65 patients, 34 (52%) were fluid responders. Baseline SvO2, CI, heart rate (HR) and mean arterial pressure (MAP) were not statistically different between groups. The responders had lower pulmonary artery occlusion pressure (PAOP) and central venous pressure (CVP) at baseline than the nonresponders. After the fluid challenge, there were no differences between the two groups in MAP, CVP, PAOP or HR. There was no correlation between changes in CI or stroke volume index and baseline SvO2. Receiver operating characteristic analysis showed that SvO2 was not a predictor of fluid responsiveness.ConclusionsThe response of septic patients to a fluid challenge is independent of baseline SvO2. The presence of a high SvO2 does not necessarily exclude the need for further fluid administration.

Peak body temperature predicts mortality in critically ill patients without cerebral damage

OBJECTIVES We investigated whether mortality in intensive care unit (ICU) patients without cerebral damage is associated with fever manifestation and characteristics. METHODS Patients admitted to a medical-surgical ICU between October 2005 and July 2006 were prospectively studied. Exclusion criteria were acute brain injury, intracerebral/subarachnoid hemorrhage, ischemic stroke, and brain surgery. An ear-based or axillary thermometer was used to measure body temperature. The association between fever (ear-based temperature, >38.3 degrees C), fever characteristics, and ICU mortality was evaluated using univariate and multivariate analysis. RESULTS Two hundred and thirty-nine patients were enrolled. Fever was not associated with ICU mortality after adjustment for confounding patient factors. A significant dose-response increase of ICU mortality according to 1 degree C increments of peak body temperature was demonstrated, whereas peak body temperature was an independent predictor of ICU mortality. CONCLUSION These findings imply that, although fever is not generally associated with mortality in patients without cerebral damage, it can be harmful and should be suppressed when it becomes very high. Rigorous clinical trials are needed to help establish antipyretic therapy guidelines.

The Use of Sodium Bicarbonate in the Treatment of Acidosis in Sepsis: A Literature Update on a Long Term Debate

Introduction. Sepsis and its consequences such as metabolic acidosis are resulting in increased mortality. Although correction of metabolic acidosis with sodium bicarbonate seems a reasonable approach, there is ongoing debate regarding the role of bicarbonates as a therapeutic option. Methods. We conducted a PubMed literature search in order to identify published literature related to the effects of sodium bicarbonate treatment on metabolic acidosis due to sepsis. The search included all articles published in English in the last 35 years. Results. There is ongoing debate regarding the use of bicarbonates for the treatment of acidosis in sepsis, but there is a trend towards not using bicarbonate in sepsis patients with arterial blood gas pH > 7.15. Conclusions. Routine use of bicarbonate for treatment of severe acidemia and lactic acidosis due to sepsis is subject of controversy, and current opinion does not favor routine use of bicarbonates. However, available evidence is inconclusive, and more studies are required to determine the potential benefit, if any, of bicarbonate therapy in the sepsis patient with acidosis.

Angiotensin II in Refractory Septic Shock

ABSTRACT Refractory septic shock is defined as persistently low mean arterial blood pressure despite volume resuscitation and titrated vasopressors/inotropes in patients with a proven or suspected infection and concomitant organ dysfunction. Its management typically requires high doses of catecholamines, which can induce significant adverse effects such as ischemia and arrhythmias. Angiotensin II (Ang II), a key product of the renin–angiotensin–aldosterone system, is a vasopressor agent that could be used in conjunction with other vasopressors to stabilize critically ill patients during refractory septic shock, and reduce catecholamine requirements. However, very few clinical data are available to support Ang II administration in this setting. Here, we review the current literature on this topic to better understand the role of Ang II administration during refractory septic shock, differentiating experimental from clinical studies. We also consider the potential role of exogenous Ang II administration in specific organ dysfunction and possible pitfalls with Ang II in sepsis. Various issues remain unresolved and future studies should investigate important topics such as: the optimal dose and timing of Ang II administration, a comparison between Ang II and the other vasopressors (epinephrine; vasopressin), and Ang II effects on microcirculation.

Hypomagnesemia in Critically Ill Sepsis Patients.

Magnesium (Mg), also known as “the forgotten electrolyte”, is the fourth most abundant cation overall and the second most abundant intracellular cation in the body. Mg deficiency has been implicated in the pathophysiology of many diseases. This article is a review of the literature regarding Mg abnormalities with emphasis on the implications of hypomagnesemia in critical illness and on treatment options for hypomagnesemia in critically ill patients with sepsis. Hypomagnesemia is common in critically ill patients, and there is strong, consistent clinical evidence, largely from observational studies, showing that hypomagnesemia is significantly associated with increased need for mechanical ventilation, prolonged ICU stay and increased mortality. Although the mechanism linking hypomagnesemia with poor clinical outcomes is not known, experimental data suggest mechanisms contributing to such outcomes. However, at the present time, there is no clear evidence that magnesium supplementation improves outcomes in critically ill patients with hypomagnesemia. Large, well-designed clinical trials are needed to evaluate the role of magnesium therapy for improving outcomes in critically ill patients with sepsis.

Prolonged high-dose intravenous magnesium therapy for severe tetanus in the intensive care unit: a case series.

IntroductionTetanus rarely occurs in developed countries, but it can result in fatal complications including respiratory failure due to generalized muscle spasms. Magnesium infusion has been used to treat spasticity in tetanus, and its effectiveness is supported by several case reports and a recent randomized controlled trial.Case presentationsThree Caucasian Greek men aged 30, 50 and 77 years old were diagnosed with tetanus and admitted to a general 12-bed intensive care unit in 2006 and 2007 for respiratory failure due to generalized spasticity. Intensive care unit treatment included antibiotics, hydration, enteral nutrition, early tracheostomy and mechanical ventilation. Intravenous magnesium therapy controlled spasticity without the need for additional muscle relaxants. Their medications were continued for up to 26 days, and adjusted as needed to control spasticity. Plasma magnesium levels, which were measured twice a day, remained in the 3 to 4.5 mmol/L range. We did not observe hemodynamic instability, arrhythmias or other complications related to magnesium therapy in these patients. All patients improved, came off mechanical ventilation, and were discharged from the intensive care unit in a stable condition.ConclusionIn comparison with previous reports, our case series contributes the following meaningful additional information: intravenous magnesium therapy was used on patients already requiring mechanical ventilation and remained effective for up to 26 days (significantly longer than in previous reports) without significant toxicity in two patients. The overall outcome was good in all our patients. However, the optimal dose, optimal duration and maximum safe duration of intravenous magnesium therapy are unknown. Therefore, until more data on the safety and efficacy of magnesium therapy are available, its use should be limited to carefully selected tetanus cases.

Pharmacokinetic Changes and Dosing Modification of Aminoglycosides in Critically Ill Obese Patients: A Literature Review

The objective of the paper is to review the literature and provide recommendations for use of aminoglycoside antibiotics in critically ill obese patients. Literature search in PubMed for all articles on the use of aminoglycosides in critically ill obese patients was conducted, and all articles related to pharmacokinetics in obesity were reviewed. Bibliographies of all searched manuscripts were also reviewed in an attempt to find additional references. Although aminoglycoside pharmacokinetics have been described in detail, data on aminoglycoside use and appropriate dose modification in critically ill obese patients are very limited. Knowledge on aminoglycoside pharmacokinetics and use in critically ill obese patients is incomplete. Pathophysiologic changes in obesity can result in sub- or supra-therapeutic aminoglycoside plasma concentrations, especially in the presence of sepsis. Rigorous clinical studies are needed to establish aminoglycoside dosing guidelines in critically ill obese patients with sepsis.