Marcin Karcz

A Novel Mitochondrial KATP Channel Assay

Rationale: The mitochondrial ATP sensitive potassium channel (mKATP) is implicated in cardioprotection by ischemic preconditioning (IPC), but the molecular identity of the channel remains controversial. The validity of current methods to assay mKATP activity is disputed. Objective: We sought to develop novel methods to assay mKATP activity and its regulation. Methods and Results: Using a thallium (Tl+)-sensitive fluorophore, we developed a novel Tl+ flux based assay for mKATP activity, and used this assay probe several aspects of mKATP function. The following key observations were made. (1) Time-dependent run down of mKATP activity was reversed by phosphatidylinositol-4,5-bisphosphate (PIP2). (2) Dose responses of mKATP to nucleotides revealed a UDP EC50 of ≈20 &mgr;mol/L and an ATP IC50 of ≈5 &mgr;mol/L. (3) The antidepressant fluoxetine (Prozac) inhibited mKATP (IC50 =2.4 &mgr;mol/L). Fluoxetine also blocked cardioprotection triggered by IPC, but did not block protection triggered by a mKATP-independent stimulus. The related antidepressant zimelidine was without effect on either mKATP or IPC. Conclusions: The Tl+ flux mKATP assay was validated by correlation with a classical mKATP channel osmotic swelling assay (R2=0.855). The pharmacological profile of mKATP (response to ATP, UDP, PIP2, and fluoxetine) is consistent with that of an inward rectifying K+ channel (KIR) and is somewhat closer to that of the KIR6.2 than the KIR6.1 isoform. The effect of fluoxetine on mKATP-dependent cardioprotection has implications for the growing use of antidepressants in patients who may benefit from preconditioning.

Preoperative thrombocytopenia and postoperative outcomes after noncardiac surgery.

Background:Most studies examining the prognostic value of preoperative coagulation testing are too small to examine the predictive value of routine preoperative coagulation testing in patients having noncardiac surgery. Methods:Using data from the American College of Surgeons National Surgical Quality Improvement database, the authors performed a retrospective observational study on 316,644 patients having noncardiac surgery who did not have clinical indications for preoperative coagulation testing. The authors used multivariable logistic regression analysis to explore the association between platelet count abnormalities and red cell transfusion, mortality, and major complications. Results:Thrombocytopenia or thrombocytosis occurred in 1 in 14 patients without clinical indications for preoperative platelet testing. Patients with mild thrombocytopenia (101,000–150,000 µl−1), moderate-to-severe thrombocytopenia (<100,000 µl−1), and thrombocytosis (≥450,000 µl−1) were significantly more likely to be transfused (7.3%, 11.8%, 8.9%, 3.1%) and had significantly higher 30-day mortality rates (1.5%, 2.6%, 0.9%, 0.5%) compared with patients with a normal platelet count. In the multivariable analyses, mild thrombocytopenia (adjusted odds ratio [AOR], 1.28; 95% CI, 1.18–1.39) and moderate-to-severe thrombocytopenia (AOR, 1.76; 95% CI, 1.49–2.08), and thrombocytosis (AOR, 1.44; 95% CI, 1.30–1.60) were associated with increased risk of blood transfusion. Mild thrombocytopenia (AOR, 1.31; 95% CI, 1.11–1.56) and moderate-to-severe thrombocytopenia (AOR, 1.93; 95% CI, 1.43–2.61) were also associated with increased risk of 30-day mortality, whereas thrombocytosis was not (AOR, 0.94; 95% CI, 0.72–1.22). Conclusion:Platelet count abnormalities found in the course of routine preoperative screening are associated with a higher risk of blood transfusion and death.

Mechanical ventilation in trauma.

Purpose of review The purpose of this review is to evaluate new concepts in mechanical ventilation in trauma. We begin with the keystone of physiology prior to embarking on a discussion of several new modes of mechanical ventilation. We will discuss the use of noninvasive ventilation as a mode to prevent intubation and then go on to airway pressure release ventilation, high-frequency oscillatory ventilation, and computer-based, closed loop ventilation. Recent findings The importance of preventing further injury in mechanical ventilation lies at the heart of the introduction of several new strategies of mechanical ventilation. New modes of ventilation have been developed to provide lung recruitment and alveolar stabilization at the lowest possible pressure. Summary The old modes of continuous positive airway pressure and bilevel positive airway pressure have been actively introduced in clinical practice in the case of trauma patients. Used with proper pain management protocols, there has been a decrease in the incidence of intubation in blunt thoracic trauma. Airway pressure release ventilation has been gaining a role in the management of thoracic injury and may lead to less incidence of physiologic trauma to mechanically ventilated patients. High-frequency oscillatory ventilation has been shown to be effective in patient care by its ability to open and recruit the lung in trauma patients and in those with acute respiratory distress syndrome but it may not have a role in patients with inhalational injury. Closed loop ventilation is a technology that may better control major pulmonary parameters and lead to more rapid titration from the ventilator to spontaneous breathing.

Acute respiratory failure complicating advanced liver disease.

Advanced liver disease is associated with hypoxemia and respiratory failure by various mechanisms. Patients with cirrhosis are especially prone to episodes of decompensation requiring intensive care unit admission and management. Such patients may already be in acute liver failure or have decompensated due to a concurrent illness such as spontaneous bacterial peritonitis, sepsis, encephalopathy, varices, or hepatorenal syndrome. Acute respiratory distress syndrome is one of the main reasons for intensive care unit admission and mortality. Overall, critically ill cirrhotic patients frequently progress to multiorgan failure requiring mechanical ventilation. Caring for such patients is therefore understandably complex and extremely challenging. Patients with end-stage liver disease are especially at risk for developing acute respiratory failure and hypoxemia secondary to hepatopulmonary syndrome, portopulmonary hypertension, and hepatic hydrothorax. They should therefore be screened for these conditions because failure to recognize and adequately treat these serious complications of cirrhosis may have devastating consequences. This article is based on a review of the current literature on how to approach and manage acute respiratory failure in advanced liver disease, which is important to intensivists, anesthesiologists, and physicians as a whole.

Noninvasive ventilation in trauma

Trauma patients are a diverse population with heterogeneous needs for ventilatory support. This requirement depends mainly on the severity of their ventilatory dysfunction, degree of deterioration in gaseous exchange, any associated injuries, and the individual feasibility of potentially using a noninvasive ventilation approach. Noninvasive ventilation may reduce the need to intubate patients with trauma-related hypoxemia. It is well-known that these patients are at increased risk to develop hypoxemic respiratory failure which may or may not be associated with hypercapnia. Hypoxemia in these patients is due to ventilation perfusion mismatching and right to left shunt because of lung contusion, atelectasis, an inability to clear secretions as well as pneumothorax and/or hemothorax, all of which are common in trauma patients. Noninvasive ventilation has been tried in these patients in order to avoid the complications related to endotracheal intubation, mainly ventilator-associated pneumonia. The potential usefulness of noninvasive ventilation in the ventilatory management of trauma patients, though reported in various studies, has not been sufficiently investigated on a large scale. According to the British Thoracic Society guidelines, the indications and efficacy of noninvasive ventilation treatment in respiratory distress induced by trauma have thus far been inconsistent and merely received a low grade recommendation. In this review paper, we analyse and compare the results of various studies in which noninvasive ventilation was applied and discuss the role and efficacy of this ventilator modality in trauma.

Blood transfusion in the perioperative period

Anemia is associated with perioperative mortality and morbidity. Since the presence of anemia and blood transfusion often go hand in hand, it can be difficult to separate the effects of anemia from the effects of perioperative transfusion. The role for blood transfusion in mitigating the mortality and morbidity associated with anemia is unclear. A restrictive transfusion strategy has been advocated for hemodynamically stable patients, as blood transfusion exposes the patient to both infectious and non-infectious complications. Further research is warranted in patients with the acute coronary syndrome, as there is insufficient evidence to make recommendations for this patient population. Additional multi-center randomized controlled trials need to be conducted in perioperative and critically ill patients with large enough sample sizes to examine differences in mortality and major complications between liberal and restrictive transfusion strategies. Further trials need to incorporate current practices in improved blood storage and leukoreduction techniques.

Respiratory Failure and Mechanical Ventilation in the Pregnant Patient

Fewer than 2% of all peripartal patients need intensive care unit admission. But due to some anatomic and physiologic changes in pregnancy, respiratory failure can be promoted. This article reviews several obstetric and nonobstetric diseases that lead to respiratory failure and the treatment of these. Furthermore, invasive and noninvasive ventilation in pregnancy is discussed and suggestions of medication during ventilation are given.

Noninvasive Ventilation in the Polytraumatized Patient

Trauma is the leading cause of death in persons younger than 44 years of age and is the fourth leading cause of death overall [1]. Approximately 140,000 trauma-related deaths occur in the United States annually. Chest trauma is the cause of death in up to one-fourth of patients with multiple-systems trauma.