Background: Despite international data indicating that Enhanced Recovery After Surgery (ERAS) programs, which combine evidence-based perioperative strategies, expedite recovery after surgery, few centers have successfully adopted this approach within the U.S. We describe the implementation and efficacy of an ERAS program for colorectal abdominal surgery in a tertiary teaching center in the U.S.Methods: We used a multi-modal and continuously evolving approach to implement an ERAS program among all patients undergoing colorectal abdominal surgery at a single hospital at the University of California, San Francisco. 279 patients who participated in the Enhanced Recovery after Surgery program were compared to 245 previous patients who underwent surgery prior to implementation of the program. Primary end points were length of stay and readmission rates. Secondary end points included postoperative pain scores, opioid consumption, postoperative nausea and vomiting, length of urinary catheterization, and time to first solid meal.Results: ERAS decreased both median total hospital length of stay (6.4 to 4.4 days) and post-procedure length of stay (6.0 to 4.1 days). 30-day all-cause readmission rates decreased from 21 to 9.4 %. Pain scores improved on postoperative day 0 (3.2 to 2.1) and day 1 (3.2 to 2.6) despite decreased opioid. Median time to first solid meal decreased from 4.7 to 2.7 days and duration of urinary catheterization decreased from 74 to 46 h. Similar improvements were observed in all other secondary end points.Conclusions: These results confirm that a multidisciplinary, iterative, team-based approach is associated with a reduction in hospital stay and an acceleration in recovery without increasing readmission rates.

University of California San Francisco, Dept of Anesthesia & Perioperative Care, San Francisco, United States

The timing of performing a tracheostomy in patients needing prolonged mechanical ventilation has been the subject of many studies over the years. This review surveys the published literature on this topic and describes the findings from the most recent multicenter randomized trials. These data are then used to form the most up-to-date conclusions regarding best practices to guide decisions on timing of tracheostomy in ventilated ICU patients.

Septic shock is the 13th leading cause of death in the United States. The rate of severe sepsis nearly doubled and mortality increased more than 60% during the 10-year period ending in 2003. Systemic inflammatory response syndrome has noninfectious and infectious causes. Noninfectious ones include burns, trauma, severe pancreatitis, and therapy with monoclonal antibodies or immunomodulatory drugs such as interleukin 2. Progression from sepsis syndrome to septic shock is caused by a series of immune responses. As an infectious injury progresses, host activation of the coagulation, immunological, and stress response systems ensues, resulting in tissue hypoperfusion and organ failure. Early studies with small numbers of patients suggest that treatment with low-dose corticosteroids has marked beneficial effects on shock reversal, the immune system, and the hemodynamic profile. Low-dose corticosteroids should only be administered to a subset of patients with septic shock who are unresponsive to fluid replacement and vasopressor therapy.

Background:We investigated the role of tandem pore potassium ion channel (K2P) TRESK in neurobehavioral function and volatile anesthetic sensitivity in genetically modified mice. Methods:Exon III of the mouse TRESK gene locus was deleted by homologous recombination using a targeting vector. The genotype of bred mice (wild type, knockout, or heterozygote) was determined using polymerase chain reaction. Morphologic and behavioral evaluations of TRESK knockout mice were compared with wild-type littermates. Sensitivity of bred mice to isoflurane, halothane, sevoflurane, and desflurane were studied by determining the minimum alveolar concentration preventing movement to tail clamping in 50% of each genotype. Results:With the exception of decreased number of inactive periods and increased thermal pain sensitivity (20% decrease in latency with hot plate test), TRESK knockout mice had healthy development and behavior. TRESK knockout mice showed a statistically significant 8% increase in isoflurane minimum alveolar concentration compared with wild-type littermates. Sensitivity to other volatile anesthetics was not significantly different. Spontaneous mortality of TRESK knockout mice after initial anesthesia testing was nearly threefold higher than that of wild-type littermates. Conclusions:TRESK alone is not critical for baseline central nervous system function but may contribute to the action of volatile anesthetics. The inhomogeneous change in anesthetic sensitivity corroborates findings in other K2P knockout mice and supports the theory that the mechanism of volatile anesthetic action involves multiple targets. Although it was not shown in this study, a compensatory effect by other K2P channels may also contribute to these observations.

Interleukin-2 (IL-2) is a cytokine that produces an in vivo immunostimulating effect when given systemically. This action may arise from stimulating the growth and expansion of cytotoxic T cells that in turn activate natural killer cells to attack tumors such as malignant melanoma and renal cell carcinoma. Therefore, administration of high-dose IL-2 can invoke an antitumor response in some patients. However, high-dose IL-2 induces severe and sometimes life-threatening toxicity, including vascular leak syndrome, hypotension, fever, and end-organ damage. Renal, hepatic, pulmonary, cardiac, and neurologic side effects have been described. Patients receiving IL-2 therefore require close monitoring to detect and treat life-threatening complications arising from treatment. The authors describe the steps taken to begin an IL-2 biotherapy program in a small ICU at a regional comprehensive cancer center. The addition of “elective” IL-2 admissions to the ICU has had a beneficial effect on stabilizing the daily census. In addition, it has brought a new cohort of patients who are highly appreciative of the care they receive and provides the nursing staff a new opportunity to develop expertise with cancer biotherapy.

Hemodynamic instability may occur during liver transplantation especially following unclamping the portal vein. A period of hypotension (postreperfusion syndrome) is usually responsive to treatment with fluids, calcium, sodium bicarbonate, and vasoactive drugs, but if hypotension persists, other causes must be sought out. In this report, we present a case in which anaphylaxis, most likely due to a component of the University of Wisconsin preservation solution, occurred coincident with liver reperfusion and severely exacerbated reperfusion hemodynamic instability. To our knowledge, this is the first report of anaphylaxis at the time of reperfusion and may provide an explanation for cases of vasoplegic syndrome associated with graft reperfusion.

General anaesthesia is administered each day to thousands of patients worldwide. Although more than 160 years have passed since the first successful public demonstration of anaesthesia, a detailed understanding of the anaesthetic mechanism of action of these drugs is still lacking. An important early observation was the Meyer-Overton correlation, which associated the potency of an anaesthetic with its lipid solubility. This work focuses attention on the lipid membrane as a likely location for anaesthetic action. With the advent of cellular electrophysiology and molecular biology techniques, tools to dissect the components of the lipid membrane have led, in recent years, to the widespread acceptance of proteins, namely receptors and ion channels, as more likely targets for the anaesthetic effect. Yet these accumulated data have not produced a comprehensive explanation for how these drugs produce central nervous system depression. In this review, we follow the story of anaesthesia mechanisms research from its historical roots to the intensely neurophysiological research regarding it today. We will also describe recent findings that identify specific neuroanatomical locations mediating the actions of some anaesthetic agents.

The two-pore-domain potassium (K2P) channels contribute to background (leak) potassium currents maintaining the resting membrane potential to play an important role in regulating neuronal excitability. As such they may contribute to nociception and the mechanism of action of volatile anesthetics. In the present study, we examined the protein expression pattern of the K2P channel TRESK in the rat central nervous system (CNS) and peripheral nervous system (PNS) by immunohistochemistry. The regional distribution expression pattern of TRESK has both similarities and significant differences from that of other K2P channels expressed in the CNS. TRESK expression is broadly found in the brain, spinal cord and dorsal root ganglia (DRG). TRESK expression is highest in important CNS structures, such as specific cortical layers, periaqueductal gray (PAG), granule cell layer of the cerebellum, and dorsal horn of the spinal cord. TRESK expression is also high in small and medium sized DRG neurons. These results provide an anatomic basis for identifying functional roles of TRESK in the rat nervous system.

The molecular site of action for volatile anesthetics remains unknown despite many years of study. Members of the K(2P) potassium channel family, whose currents are potentiated by volatile anesthetics have emerged as possible anesthetic targets. In fact, a mouse model in which the gene for TREK-1 (KCNK2) has been inactivated shows resistance to volatile anesthetics. In this study we tested whether inactivation of another member of this ion channel family, KCNK7, in a knockout mouse displayed altered sensitivity to the anesthetizing effect of volatile anesthetics. KCNK7 knockout mice were produced by standard gene inactivation methods. Heterozygous breeding pairs produced animals that were homozygous, heterozygous or wild-type for the inactivated gene. Knockout animals were tested for movement in response to noxious stimulus (tail clamp) under varying concentrations of isoflurane, halothane, and desflurane to define the minimum alveolar concentration (MAC) preventing movement. Mice homozygous for inactivated KCNK7 were viable and indistinguishable in weight, general development and behavior from heterozygotes or wild-type littermates. Knockout mice (KCNK7-/-) displayed no difference in MAC for the three volatile anesthetics compared to heterozygous (+/-) or wild-type (+/+) littermates. Because inactivation of KCNK7 does not alter MAC, KCNK7 may play only a minor role in normal CNS function or may have had its function compensated for by other inhibitory mechanisms. Additional studies with transgenic animals will help define the overall role of the K(2P) channels in normal neurophysiology and in volatile anesthetic mechanisms.

UCSF–Anesthesia and Perioperative Care, San Francisco, CA The authors have not disclosed any potential conflicts of interest.

K2P channels are a family of cellular proteins that are essential for electrical signaling throughout the body. There are six K2P channel subfamilies, consisting of 15 distinct mammalian genes. K2P channels display a remarkable range of regulation by cellular, physical and pharmacologic agents, including protein kinases, intracellular Ca2+, changes in internal and external pH, anesthetic agents, heat, stretch and membrane deformers. The molecular and cellular mechanisms underlying this regulation are complex and cooperate at many different levels. Recent research has provided strong evidence that the spatiotemporal-specific expression of K2P channels are determinants of physiologic selectivity and specificity. In recent years, knockout mice have been generated with inactivated K2P channel genes. These animals shed new light on the contribution of K2P channels to normal and abnormal physiology. In this review, we summarize the published data on these mice to broaden the understanding of the role of K2P channel activity.