Peripheral Nervous System Pain Modulation.

The percutaneous technique of electrode insertion in the vicinity of the greater occipital nerves to treat occipital neuralgia was first described in the 1990s by Weiner and Reed. This subsequently stimulated awareness of peripheral nerve stimulation (PNS). The more recent advent emergence of a minimally invasive percutaneous approach by way of using ultrasound has further increased the interest in PNS as a viable alternative to more invasive techniques. PNS has become more popular recently and is increasingly used to treat various pain conditions. Its foundation is fundamentally based on the gate control theory, although the precise mechanism underlying its analgesic effect is still indefinite. Studies have demonstrated the peripheral and central analgesic mechanisms of PNS by modulating the inflammatory pathways, the autonomic nervous system, the endogenous pain inhibition pathways, and the involvement of the cortical and subcortical areas. Peripheral nerve stimulation exhibits its neuromodulatory effect both peripherally and centrally. Further understanding of the modulation of PNS mechanisms can help guide stimulation approaches and parameters to optimize the use of PNS. his chapter aims to review the background and mechanisms of PNS modulation. PNS is becoming one of the most diverse therapies in neuromodulation due to rapid evolution and expansion. It is an attractive option for clinicians due to the simplicity and versatility of procedures that can be combined with other neuromodulation treatments or used alone. It has a distinct role in the modulation of functional conditions.

Non-Invasive Mechanical Ventilation in Critically Ill Trauma Patients: A Systematic Review.

There is limited literature on non-invasive mechanical ventilation (NIMV) in patients with polytrauma-related acute respiratory failure (ARF). Despite an increasing worldwide application, there is still scarce evidence of significant NIMV benefits in this specific setting, and no clear recommendations are provided. We performed a systematic review, and a search of clinical databases including MEDLINE and EMBASE was conducted from the beginning of 1990 until today. Although the benefits in reducing the intubation rate, morbidity and mortality are unclear, NIMV may be useful and does not appear to be associated with harm when applied in properly selected patients with moderate ARF at an earlier stage of injury by experienced teams and in appropriate settings under strict monitoring. In the presence of these criteria, NIMV is worth attempting, but only if endotracheal intubation is promptly available because non-responders to NIMV are burdened by an increased mortality when intubation is delayed.

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 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.

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), moderate-to-severe thrombocytopenia (<100,000 µl), and thrombocytosis (≥450,000 µl) 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.

Role of p90(RSK) in regulating the Crabtree effect: implications for cancer.

High glucose inhibits mitochondrial respiration, known as the 'Crabtree effect', in cancer cells and possibly other cell types. The upstream pathways regulating this phenomenon are poorly understood. In diabetes, where glucose levels are elevated, the p90(RSK) (p90 ribosomal S6 kinase) has received much attention as a potential upstream mediator of the effects of high glucose. Evidence is also emerging that p90(RSK) may play a role in cancer cell signalling, although the role of p90(RSK) in regulating cancer cell metabolism is unclear. In the present paper, we provide an overview of the Crabtree effect and its relationship to mitochondrial metabolism. Furthermore, preliminary data are presented suggesting a role for p90(RSK) and its upstream components, the ERK (extracellular-signal-regulated kinase) family of MAPKs (mitogen-activated protein kinases), in the Crabtree effect.

Respiratory complications in the postanesthesia care unit: A review of pathophysiological mechanisms.

General anesthesia and mechanical ventilation impair pulmonary function, even in normal individuals, and result in decreased oxygenation in the postanesthesia period. They also cause a reduction in functional residual capacity of up to 50% of the preanesthesia value. It has been shown that pulmonary atelectasis is a common finding in anesthetized individuals because it occurs in 85% to 90% of healthy adults. Furthermore, there is substantial evidence that atelectasis, in combination with alveolar hypoventilation and ventilation-perfusion mismatch, is the core mechanism responsible for postoperative hypoxemic events in the majority of patients in the postanesthesia care unit (PACU). Many concomitant factors also must be considered, such as respiratory depression from the type and anatomical site of surgery altering lung mechanics, the consequences of hemodynamic impairment and the residual effects of anesthetic drugs, most notably residual neuromuscular blockade. The appropriate use of anesthetic and analgesic techniques, when combined with meticulous postoperative care, clearly influences pulmonary outcomes in the PACU. The present review emphasizes the major pathophysiological mechanisms and treatment strategies of critical respiratory events in the PACU to provide health care workers with the knowledge needed to prevent such potentially adverse outcomes from occurring.

L'anesthésie générale et la ventilation mécanique nuisent à la fonction pulmonaire, même chez des personnes en santé, et entraînent une diminution de l'oxygénation pendant la période postanesthésique. Elles provoquent également une réduction de la capacité fonctionnelle résiduelle pouvant atteindre 50 % de la valeur obtenue avant l'anesthésie. Il a été démontré que l'atélectasie pulmonaire est courante chez les personnes anesthésiées. En effet, elle se produit chez 85 % à 90 % des adultes en santé. De plus, il est clairement démontré que l'atélectasie, associée à l'hypoventilation alvéolaire et à la discordance entre la ventilation et la perfusion, est le principal mécanisme responsable d'événements hypoxémiques postopératoires chez la majorité des patients de l'unité de soins postanesthésiques (USPA). Il faut également tenir compte de nombreux facteurs concomitants, tels que la dépression respiratoire causée par le type et le foyer anatomique des mécaniques pulmonaires modifiées par chirurgie, les conséquences d'une atteinte hémodynamique et les effets résiduels des médicaments anesthésiques, notamment le blocage neuromusculaire résiduel. Le recours pertinent aux techniques anesthésiques et analgésiques, associé à des soins postopératoires méticuleux, influe clairement sur les issues pulmonaires à l'USPA. La présente analyse fait ressortir les principaux mécanismes physiopathologiques et stratégies thérapeutiques d'événements respiratoires critiques à l'USPA pour transmettre aux dispensateurs de soins les connaissances nécessaires en vue d'éviter la survenue d'issues indésirables.

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.

Lungs in critical care: new look at old practices.

There has been a marked increase in the volume of critical care services throughout the world in the last few years with the wide addition of intensive care units in developing nations. Despite extensive efforts in research and some progress in treatment, mortality and morbidity have not significantly decreased. Recent research has demonstrated that modifying standard practices of mechanical ventilation and sedation may contribute to improved patient outcomes. This article discusses how new aspects of physiologically based mechanical ventilation with minimal intravenous sedation may help decrease the incidence of nosocomial pneumonia, modulate systemic inflammatory response, and reduce the incidence of delirium. These interlinked modalities may someday contribute to decreased length of stay and a reduction in treatment-related complications. These concepts may also open new avenues to improve patient care and stimulate ongoing investigation in other areas related to physiologically based critical care practices.

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.

An ex-vivo model for hypothermic pulsatile perfusion of porcine pancreata: hemodynamic and morphologic characteristics.

OBJECTIVES: Hypothermic machine perfusion is a well-established preservation method for kidneys that allows for better preservation over longer periods and pretransplant assessment of graft viability. This technique has only sporadically been used for pancreatic grafts. The aim of this study was to establish a hypothermic machine perfusion model for porcine pancreas perfusion. MATERIALS AND METHODS: Fifteen porcine pancreata were subjected to 25 minutes of warm ischemia and 149 minutes of cold ischemia before undergoing meticulous bench work preparation and perfusion, via an aortic segment, on the RM3 perfusion machine with University of Wisconsin (Barr Laboratories Inc., Pomona, NY, USA) solution. Perfusion variables (degrees C, temperature; mm Hg, systolic perfusion pressure; mL/min, flow volume; mm Hg/mL/min, resistance) were recorded every 30 minutes. Tissue samples were assessed for each pancreas preperfusion and postperfusion using a semiquantitative scoring scale to grade histopathologic changes: acinar cell damage (0-4), islet cell damage (0-3), inflammation (0-3), and edema (0-3). RESULTS: Hypothermic machine perfusion time was set at 315 minutes, and all grafts were maintained between 4-10 degrees C. The results were as follows (range, mean -/+ SD): systolic perfusion pressures were 5-13 mm Hg (9.61 -/+ 3.25 mm Hg) during the first 60 minutes (priming), and 15-23 mm Hg (21.07 -/+ 4.26 mm Hg) during the maintenance period. Target flow volumes reached 141-152 mL/min (147.6 -/+ 8.969 mL/min) at 60 pulses per minute. Intrapancreatic resistance decreased throughout priming to 0.03-0.09 mm Hg/mL/min (0.083 -/+ 0.042 mm Hg/mL/min), and remained unchanged until completion of perfusion. Pancreatic weight increase varied from 3.2% to 18.3% (13.36% -/+ 4.961%). There was significant postperfusion reduction in islet and acinar cell damage (P = .001 and P = .01 respectively). CONCLUSIONS: We have developed a model of machine perfusion for porcine pancreata which is simple, reliable, and protects graft histopathologic integrity. The model can be used in further studies to improve the quality of pancreas preservation, and assess and improve the viability of the condition of borderline pancreatic grafts.

A novel mitochondrial K(ATP) channel assay.

RATIONALE: The mitochondrial ATP sensitive potassium channel (mK(ATP)) is implicated in cardioprotection by ischemic preconditioning (IPC), but the molecular identity of the channel remains controversial. The validity of current methods to assay mK(ATP) activity is disputed. OBJECTIVE: We sought to develop novel methods to assay mK(ATP) activity and its regulation. METHODS AND RESULTS: Using a thallium (Tl(+))-sensitive fluorophore, we developed a novel Tl(+) flux based assay for mK(ATP) activity, and used this assay probe several aspects of mK(ATP) function. The following key observations were made. (1) Time-dependent run down of mK(ATP) activity was reversed by phosphatidylinositol-4,5-bisphosphate (PIP(2)). (2) Dose responses of mK(ATP) to nucleotides revealed a UDP EC(50) of approximately 20 micromol/L and an ATP IC(50) of approximately 5 micromol/L. (3) The antidepressant fluoxetine (Prozac) inhibited mK(ATP) (IC(50)=2.4 micromol/L). Fluoxetine also blocked cardioprotection triggered by IPC, but did not block protection triggered by a mK(ATP)-independent stimulus. The related antidepressant zimelidine was without effect on either mK(ATP) or IPC. CONCLUSIONS: The Tl(+) flux mK(ATP) assay was validated by correlation with a classical mK(ATP) channel osmotic swelling assay (R(2)=0.855). The pharmacological profile of mK(ATP) (response to ATP, UDP, PIP(2), and fluoxetine) is consistent with that of an inward rectifying K(+) channel (K(IR)) and is somewhat closer to that of the K(IR)6.2 than the K(IR)6.1 isoform. The effect of fluoxetine on mK(ATP)-dependent cardioprotection has implications for the growing use of antidepressants in patients who may benefit from preconditioning.

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.