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Although short-term machine perfusion (-24 h) allows for resuscitation and viability assessment of high-risk donor livers, the donor organ shortage might be further remedied by long-term perfusion machines. Extended preservation of injured donor livers may allow reconditioning, repairing, and regeneration. This review summarizes the necessary requirements and challenges for long-term liver machine preservation, which requires integrating multiple core physiological functions to mimic the physiological environment inside the body. A pump simulates the heart in the perfusion system, including automatically controlled adjustment of flow and pressure settings. Oxygenation and ventilation are required to account for the absence of the lungs combined with continuous blood gas analysis. To avoid pressure necrosis and achieve heterogenic tissue perfusion during preservation, diaphragm movement should be simulated. An artificial kidney is required to remove waste products and control the perfusion solution's composition. The perfusate requires an oxygen carrier, but will also be challenged by coagulation and activation of the immune system. The role of the pancreas can be mimicked through closed-loop control of glucose concentrations by automatic injection of insulin or glucagon. Nutrients and bile salts, generally transported from the intestine to the liver, have to be supplemented when preserving livers long term. Especially for long-term perfusion, the container should allow maintenance of sterility. In summary, the main challenge to develop a long-term perfusion machine is to maintain the liver's homeostasis in a sterile, carefully controlled environment. Long-term machine preservation of human livers may allow organ regeneration and repair, thereby ultimately solving the shortage of donor livers. [ABSTRACT FROM AUTHOR]

Here, we provide an overview of the concept of a lactate-protected hypoglycemia ("LPH"), originally proposed as lowering glucose while simultaneously increasing lactate concentration as a method by which tumors might be targeted. Central to this hypothesis is that lactate can act as a critical salvage fuel for the central nervous system, allowing for wide perturbations in whole body and central nervous system glucose concentrations. Further, many tumors exhibit "the Warburg" effect, consuming glucose and producing and exporting lactate despite adequate oxygenation. While some recent data have provided evidence for a "reverse-Warburg," where some tumors may preferentially consume lactate, many of these experimental methods rely on a significant elevation in lactate in the tumor microenvironment. To date it remains unclear how various tumors behave in vivo , and how they might respond to perturbations in lactate and glucose concentrations or transport inhibition. By exploiting and targeting lactate transport and metabolism in tumors (with a combination of changes in lactate and glucose concentrations, transport inhibitors, etc.), we can begin developing novel methods for targeting otherwise difficult to treat pathologies in the brain and spinal cord. Here we discuss evidence both experimental and observational, and provide direction for next steps in developing therapies based on these concepts. [ABSTRACT FROM AUTHOR]

Byline: Marjolijn N. de Hooge (1), Bas H. Verhoeven (2), Willem J. M. J. Rutten (1), Maarten W. N. Nijsten (2) Author Affiliation: (1) Hospital Pharmacy, Groningen University Hospital, PO Box 30.001, 9700 RB, Groningen, The Netherlands (2) Surgical Intensive Care Unit, Groningen University Hospital, 9700 RB, Groningen, The Netherlands Article History: Received Date: 12/10/2002 Accepted Date: 06/12/2002 Article note: Electronic Publication

Over thousands of years it has been thought that the moon influences human behaviour and the world around us. We reviewed the literature for evidence of a relation of the lunar cycle with the incidence of trauma. We searched Pubmed for studies relating the moon and its phases to trauma. Nine studies were found, of which one suggested an inverse relation of full moon with the incidence of trauma. The lunar cycle might influence trauma incidence, but if any real effect exists, it is certainly small. Moreover such an effect does not require paranormal explanations. [ABSTRACT FROM AUTHOR]

The article discusses a study which determined the prognostic value of myocardial blush grade (MBG) during primary percutaneous coronary intervention (PCI) in consecutive patients with ST-elevation myocardial infarction (STEMI). The study included patients with STEMI who underwent primary PCI between January 2004 and July 2008. Study authors concluded that MBG scored by the operator during primary PCI can be used as a prognostic factor for 1-year all cause mortality in patients with STEMI.

Background: Potassium disorders can cause major complications and must be avoided in critically ill patients. Regulation of potassium in the intensive care unit (ICU) requires potassium administration with frequent blood potassium measurements and subsequent adjustments of the amount of potassium administrated. The use of a potassium replacement protocol can improve potassium regulation. For safety and efficiency, computerized protocols appear to be superior over paper protocols. The aim of this study was to evaluate if a computerized potassium regulation protocol in the ICU improved potassium regulation. Methods: In our surgical ICU (12 beds) and cardiothoracic ICU (14 beds) at a tertiary academic center, we implemented a nurse-centered computerized potassium protocol integrated with the pre-existent glucose control program called GRIP (Glucose Regulation in Intensive Care patients). Before implementation of the computerized protocol, potassium replacement was physician-driven. Potassium was delivered continuously either by central venous catheter or by gastric, duodenal or jejunal tube. After every potassium measurement, nurses received a recommendation for the potassium administration rate and the time to the next measurement. In this before-after study we evaluated potassium regulation with GRIP. The attitude of the nursing staff towards potassium regulation with computer support was measured with questionnaires. Results: The patient cohort consisted of 775 patients before and 1435 after the implementation of computerized potassium control. The number of patients with hypokalemia (<3.5 mmol/L) and hyperkalemia (>5.0 mmol/L) were recorded, as well as the time course of potassium levels after ICU admission. The incidence of hypokalemia and hyperkalemia was calculated. Median potassium-levels were similar in both study periods, but the level of potassium control improved: the incidence of hypokalemia decreased from 2.4% to 1.7% (P < 0.001) and hyperkalemia from 7.4% to 4.8% (P < 0.001). Nurses indicated that they considered computerized potassium control an improvement over previous practice. Conclusions: Computerized potassium control, integrated with the nurse-centered GRIP program for glucose regulation, is effective and reduces the prevalence of hypo- and hyperkalemia in the ICU compared with physician-driven potassium regulation. [ABSTRACT FROM AUTHOR]

Background: Potassium depletion is common in hospitalized patients and can cause serious complications such as cardiac arrhythmias. In the intensive care unit (ICU) the majority of patients require potassium suppletion. However, there are no data regarding the optimal control target in critically ill patients. After open-heart surgery, patients have a strongly increased risk of atrial fibrillation or atrial flutter (AFF). In a novel trial design, we examined if in these patients different potassium control-targets within the normal range may have different effects on the incidence of AFF. Methods/Design: The "computer-driven Glucose and potassium Regulation program in Intensive care Patients with COMparison of PotASSium targets within normokalemic range (GRIP-COMPASS) trial" is a single-center prospective trial in which a total of 1200 patients are assigned to either a potassium control-target of 4.0 mmol/L or 4.5 mmol/L in consecutive alternating blocks of 50 patients each. Potassium levels are regulated by the computer-assisted potassium suppletion algorithm called GRIP-II (Glucose and potassium regulation for Intensive care Patients). Primary endpoint is the in-hospital incidence of AFF after cardiac surgery. Secondary endpoints are: in-hospital AFF in medical patients or patients after non-cardiac surgery, actually achieved potassium levels and their variation, electrolyte and glucose levels, potassium and insulin requirements, cumulative fluid balance, (ICU) length of stay, ICU mortality, hospital mortality and 90-day mortality. Discussion: The GRIP-COMPASS trial is the first controlled clinical trial to date that compares potassium targets. Other novel methodological elements of the study are that it is performed in ICU patients where both targets are within the normal range and that a computer-assisted potassium suppletion algorithm is used. Trial registration: NCT 01085071 at ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

The article presents a study which estimates the mortality risk to patients with trauma. Result shows that emergency trauma score (EMTRAS) from the emergency room predicts mortality. It notes that knowledge of the anatomical injuries are not necessary. It also suggests that determination of EMTRAS will inform caregivers on the severity on the condition of patients with trauma.

Background: In patients who are weaned with a tracheostomy tube (TT), continuous positive airway pressure (CPAP) is frequently used. Dedicated CPAP systems or ventilators with bulky tubing are usually applied. However, CPAP can also be effective without a ventilator by the disposable Boussignac CPAP (BCPAP) system that is normally used with face masks. Objective:It was the aim of this audit to evaluate the feasibility of low-level BCPAP in patients who were weaned with a TT. Methods: All patients at our surgical intensive care unit who received a TT for weaning were considered for application of BCPAP. Once patients had received minimal pressure support from the mechanical ventilator, the BCPAP device was connected to the TT three times a day for 30 min with pressure set to 3–5 cm H2O, FiO2 at 0.4 and with humidification. BCPAP was then gradually extended to 24 h/day. Patient acceptance, complications and outcome were recorded. Results: 58 patients received a TT to facilitate weaning. They had a median stay of 52 days in the intensive care unit during which they had an endotracheal tube for 22 days and a TT for 28 days. 50 of these patients (86%) received BCPAP for a median of 16 days. The lightweight BCPAP system was well tolerated without tube obstructions or accidental decannulations and may have contributed to patient mobility. No patient remained on ventilatory support after hospital discharge. In-hospital and 1-year survival were 86 and 71%, respectively. Conclusions: BCPAP is a feasible and safe method for weaning tracheostomy patients. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Continuous positive airway pressure (CPAP) treatment for acute cardiogenic pulmonary edema can have important benefits in acute cardiac care. However, coronary care units are usually not equipped and their personnel not adequately trained for applying CPAP with mechanical ventilators. Therefore we investigated in the coronary care unit setting the feasibility and outcome of the simple Boussignac mask-CPAP (BCPAP) system that does not need a mechanical ventilator. Methods: BCPAP was introduced in a coronary care unit where staff had no CPAP experience. All consecutive patients transported to our hospital with acute cardiogenic pulmonary edema, a respiratory rate > 25 breaths/min and a peripheral arterial oxygen saturation of < 95% while receiving oxygen, were included in a prospective BCPAP group that was compared with a historical control group that received conventional treatment with oxygen alone. Results: During the 2-year prospective BCPAP study period 108 patients were admitted with acute cardiogenic pulmonary edema. Eighty-four of these patients (78%) were treated at the coronary care unit of which 66 (61%) were treated with BCPAP. During the control period 66 patients were admitted over a 1-year period of whom 31 (47%) needed respiratory support in the intensive care unit. BCPAP treatment was associated with a reduced hospital length of stay and fewer transfers to the intensive care unit for intubation and mechanical ventilation. Overall estimated savings of approximately € 3,800 per patient were achieved with the BCPAP strategy compared to conventional treatment. Conclusion: At the coronary care unit, BCPAP was feasible, medically effective, and cost-effective in the treatment of acute cardiogenic pulmonary edema. Endpoints included mortality, coronary care unit and hospital length of stay, need of ventilatory support, and cost (savings). [ABSTRACT FROM AUTHOR]

Background: Favorable clinical outcomes have been observed with glucose-insulin-potassium infusion (GIK) in acute myocardial infarction (MI). The mechanisms of this beneficial effect have not been delineated clearly. GIK has metabolic, anti-inflammatory and profibrinolytic effects and it may preserve the ischemic myocardium. We sought to assess the effect of GIK infusion on infarct size and left ventricular function, as part of a randomized controlled trial. Methods: Patients (n = 940) treated for acute MI by primary percutaneous coronary intervention (PCI) were randomized to GIK infusion or no infusion. Endpoints were the creatinine kinase MB-fraction (CK-MB) and left ventricular ejection fraction (LVEF). CK-MB levels were determined 0, 2, 4, 6, 24, 48, 72 and 96 hours after admission and the LVEF was measured before discharge. Results: There were no differences between the two groups in the time course or magnitude of CK-MB release: the peak CK-MB level was 249 ± 228 U/L in the GIK group and 240 ± 200 U/L in the control group (NS). The mean LVEF was 43.7 ± 11.0 % in the GIK group and 42.4 ± 11.7% in the control group (P = 0.12). A LVEF ≤ 30% was observed in 18% in the controls and in 12% of the GIK group (P = 0.01). Conclusion: Treatment with GIK has no effect on myocardial function as determined by LVEF and by the pattern or magnitude of enzyme release. However, left ventricular function was preserved in GIK treated patients. [ABSTRACT FROM AUTHOR]

Oxygenated ex situ machine perfusion of donor livers is an alternative for static cold preservation that can be performed at temperatures from 0 °C to 37 °C. Organ metabolism depends on oxygen to produce adenosine triphosphate and temperatures below 37 °C reduce the metabolic rate and oxygen requirements. The transport and delivery of oxygen in machine perfusion are key determinants in preserving organ viability and cellular function. Oxygen delivery is more challenging than carbon dioxide removal, and oxygenation of the perfusion fluid is temperature dependent. The maximal oxygen content of water-based solutions is inversely related to the temperature, while cellular oxygen demand correlates positively with temperature. Machine perfusion above 20 °C will therefore require an oxygen carrier to enable sufficient oxygen delivery to the liver. Human red blood cells are the most physiological oxygen carriers. Alternative artificial oxygen transporters are hemoglobin-based oxygen carriers, perfluorocarbons, and an extracellular oxygen carrier derived from a marine invertebrate. We describe the principles of oxygen transport, delivery, and consumption in machine perfusion for donor livers using different oxygen carrier-based perfusion solutions and we discuss the properties, advantages, and disadvantages of these carriers and their use. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Hypernatremia in critically ill patients" by G. Lindner and G. C. Funk in the 2013 issue.