Continuous flow left ventricular assist devices: a valid option for heart failure patients

Recent outstanding clinical advances with new mechanical circulatory systems (MCS) have led to additional strategies in the treatment of end stage heart failure (HF). Heart transplantation (HTx) can be postponed and for certain patients even replaced by smaller implantable left ventricular assist devices (LVAD). Mechanical support of the failing left ventricle enables appropriate hemodynamic stabilisation and recovery of secondary organ failure, often seen in these severely ill patients. These new devices may be of great help to bridge patients until a suitable cardiac allograft is available but are also discussed as definitive treatment for patients who do not qualify for transplantation. Main indications for LVAD implantation are bridge to recovery, bridge to transplantation or destination therapy. LVAD may be an important tool for patients with an expected prolonged period on the waiting list, for instance those with blood group 0 or B, with a body weight over 90 kg and those with potentially reversible secondary organ failure and pulmonary artery hypertension. However, LVAD implantation means an additional heart operation with inherent peri-operative risks and complications during the waiting period. Finally, cardiac transplantation in patients with prior implantation of a LVAD represents a surgical challenge. This review summarises the current knowledge about LVAD and continuous flow devices especially since the latter have been increasingly used worldwide in the most recent years. The review is also based on the institutional experience at Berne University Hospital between 2000 and 2012. Apart from short-term devices (Impella, Cardiac Assist, Deltastream and ECMO) which were used in approximately 150 cases, 85 pulsatile long-term LVAD, RVAD or bi-VAD and 44 non-pulsatile LVAD (mainly HeartMateII and HeartWare) were implanted. After an initial learning curve, one-year mortality dropped to 10.4% in the last 58 patients.

TONOMETRY REVISITED: PERFUSION-RELATED, METABOLIC, AND RESPIRATORY COMPONENTS OF GASTRIC MUCOSAL ACIDOSIS IN ACUTE CARDIORESPIRATORY FAILURE

Mucosal pH (pHi) is influenced by local perfusion and metabolism (mucosal-arterial Pco2 gradient, DeltaPco2), systemic metabolic acidosis (arterial bicarbonate), and respiration (arterial Pco2). We determined these components of pHi and their relation to outcome during the first 24 h of intensive care. We studied 103 patients with acute respiratory or circulatory failure (age, 63 +/- 2 [mean +/- SEM]; Acute Physiology and Chronic Health Evaluation II score, 20 +/- 1; Sequential Organ Failure Assessment score, 8 +/- 0). pHi, and the effects of bicarbonate and arterial and mucosal Pco2 on pHi, were assessed at admission, 6, and 24 h. pHi was reduced (at admission, 7.27 +/- 0.01) due to low arterial bicarbonate and increased DeltaPco2. Low pHi (<7.32) at admission (n = 58; mortality, 29% vs. 13% in those with pHi >/=7.32 at admission; P = 0.061) was associated with an increased DeltaPco2 in 59% of patients (mortality, 47% vs. 4% for patients with low pHi and normal DeltaPco2; P = 0.0003). An increased versus normal DeltaPco2, regardless of pHi, was associated with increased mortality at admission (51% vs. 5%; P < 0.0001; n = 39) and at 6 h (34% vs. 13%; P = 0.016; n = 45). A delayed normalization or persistently low pHi (n = 47) or high DeltaPco2 (n = 25) was associated with high mortality (low pHi [34%] vs. high DeltaPco2 [60%]; P = 0.046). In nonsurvivors, hypocapnia increased pHi at baseline, 6, and 24 h (all P

Intravascular oxygenation for advanced respiratory failure

Severe acute respiratory failure of varying etiology may require the temporary use of artificial gas exchange devices. So far, extracorporeal membrane oxygenation and extracorporeal carbon dioxide removal have been used successfully for this purpose. A totally implantable intravascular oxygenator (IVOX) recently became available. The authors have used IVOX in three patients who presented with severe respiratory failure secondary to pneumonia (n = 2) and post-traumatic adult respiratory distress syndrome (n = 1). At the time of implantation, all patients had hypoxemia (PaO2 less than 60) despite a 100% inspired oxygen concentration and forced mechanical ventilation. The duration of IVOX therapy ranged from 12 to 71 hr. All patients initially showed improvement in arterial oxygenation, allowing for moderate reduction of ventilator therapy after several hours. In one patient the pulmonary status deteriorated further, and she died from multiple organ failure despite IVOX therapy. One patient could be stabilized but died from other causes. The third patient is a long-term survivor 18 months after IVOX therapy. Gas transfer capabilities of IVOX are limited when compared to extracorporeal membrane oxygenation, and this may restrict its clinical applicability in cases of severe adult respiratory distress syndrome. However, IVOX may be used successfully in selected patients with less severe respiratory failure.

Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis

BACKGROUND & AIMS Patients with cirrhosis hospitalized for an acute decompensation (AD) and organ failure are at risk for imminent death and considered to have acute-on-chronic liver failure (ACLF). However, there are no established diagnostic criteria for ACLF, so little is known about its development and progression. We aimed to identify diagnostic criteria of ACLF and describe the development of this syndrome in European patients with AD. METHODS We collected data from 1343 hospitalized patients with cirrhosis and AD from February to September 2011 at 29 liver units in 8 European countries. We used the organ failure and mortality data to define ACLF grades, assess mortality, and identify differences between ACLF and AD. We established diagnostic criteria for ACLF based on analyses of patients with organ failure (defined by the chronic liver failure-sequential organ failure assessment [CLIF-SOFA] score) and high 28-day mortality rate (>15%). RESULTS Of the patients assessed, 303 had ACLF when the study began, 112 developed ACLF, and 928 did not have ACLF. The 28-day mortality rate among patients who had ACLF when the study began was 33.9%, among those who developed ACLF was 29.7%, and among those who did not have ACLF was 1.9%. Patients with ACLF were younger and more frequently alcoholic, had more associated bacterial infections, and had higher numbers of leukocytes and higher plasma levels of C-reactive protein than patients without ACLF (P < .001). Higher CLIF-SOFA scores and leukocyte counts were independent predictors of mortality in patients with ACLF. In patients without a prior history of AD, ACLF was unexpectedly characterized by higher numbers of organ failures, leukocyte count, and mortality compared with ACLF in patients with a prior history of AD. CONCLUSIONS We analyzed data from patients with cirrhosis and AD to establish diagnostic criteria for ACLF and showed that it is distinct from AD, based not only on the presence of organ failure(s) and high mortality rate but also on age, precipitating events, and systemic inflammation. ACLF mortality is associated with loss of organ function and high leukocyte counts. ACLF is especially severe in patients with no prior history of AD.

Clinical Course of acute-on-chronic liver failure syndrome and effects on prognosis

Acute-on-chronic liver failure (ACLF) is characterized by acute decompensation (AD) of cirrhosis, organ failure(s), and high 28-day mortality. We investigated whether assessments of patients at specific time points predicted their need for liver transplantation (LT) or the potential futility of their care. We assessed clinical courses of 388 patients who had ACLF at enrollment, from February through September 2011, or during early (28-day) follow-up of the prospective multicenter European Chronic Liver Failure (CLIF) ACLF in Cirrhosis study. We assessed ACLF grades at different time points to define disease resolution, improvement, worsening, or steady or fluctuating course. ACLF resolved or improved in 49.2%, had a steady or fluctuating course in 30.4%, and worsened in 20.4%. The 28-day transplant-free mortality was low-to-moderate (6%-18%) in patients with nonsevere early course (final no ACLF or ACLF-1) and high-to-very high (42%-92%) in those with severe early course (final ACLF-2 or -3) independently of initial grades. Independent predictors of course severity were CLIF Consortium ACLF score (CLIF-C ACLFs) and presence of liver failure (total bilirubin ≥12 mg/dL) at ACLF diagnosis. Eighty-one percent had their final ACLF grade at 1 week, resulting in accurate prediction of short- (28-day) and mid-term (90-day) mortality by ACLF grade at 3-7 days. Among patients that underwent early LT, 75% survived for at least 1 year. Among patients with ≥4 organ failures, or CLIF-C ACLFs >64 at days 3-7 days, and did not undergo LT, mortality was 100% by 28 days. CONCLUSIONS Assessment of ACLF patients at 3-7 days of the syndrome provides a tool to define the emergency of LT and a rational basis for intensive care discontinuation owing to futility.

Organ inflammation in porcine Escherichia coli sepsis is markedly attenuated by combined inhibition of C5 and CD14.

Sepsis is an infection-induced systemic inflammatory syndrome, potentially causing organ failure. We previously showed attenuating effects on inflammation, thrombogenicity and haemodynamics by inhibiting the Toll-like receptor co-factor CD14 and complement factor C5 in a porcine Escherichia coli-induced sepsis model. The present study explored the effect on organ inflammation in these pigs. Tissue samples were examined from the combined treatment group (n = 8), the positive (n = 8) and negative (n = 6) control groups after 4h of sepsis. Inflammatory biomarkers were measured using ELISA, multiplex and qPCR analysis. Combined inhibition of C5 and CD14 markedly attenuated IL-1β by 31-66% (P < 0.05) and IL-6 by 54-96% (P < 0.01) in liver, kidney, lung and spleen; IL-8 by 65-100% in kidney, lung, spleen, and heart (P < 0.05) and MCP-1 by 46-69% in liver, kidney, spleen and heart (P < 0.05). Combined inhibition significantly attenuated tissue factor mRNA upregulation in spleen (P < 0.05) and IP-10 mRNA upregulation in four out of five organs. Finally, C5aR mRNA downregulation was prevented in heart and kidney (P < 0.05). Combined inhibition of C5 and CD14 thus markedly attenuated inflammatory responses in all organs examined. The anti-inflammatory effects observed in lung and heart may explain the delayed haemodynamic disturbances observed in septic pigs receiving combined inhibition of C5 and CD14.

Levosimendan for the Prevention of Acute Organ Dysfunction in Sepsis

BACKGROUND Levosimendan is a calcium-sensitizing drug with inotropic and other properties that may improve outcomes in patients with sepsis. 
METHODS We conducted a double-blind, randomized clinical trial to investigate whether levosimendan reduces the severity of organ dysfunction in adults with sepsis. Patients were randomly assigned to receive a blinded infusion of levosimendan (at a dose of 0.05 to 0.2 μg per kilogram of body weight per minute) for 24 hours or placebo in addition to standard care. The primary outcome was the mean daily Sequential Organ Failure Assessment (SOFA) score in the intensive care unit up to day 28 (scores for each of five systems range from 0 to 4, with higher scores indicating more severe dysfunction; maximum score, 20). Secondary outcomes included 28-day mortality, time to weaning from mechanical ventilation, and adverse events. 
RESULTS The trial recruited 516 patients; 259 were assigned to receive levosimendan and 257 to receive placebo. There was no significant difference in the mean (±SD) SOFA score between the levosimendan group and the placebo group (6.68±3.96 vs. 6.06±3.89; mean difference, 0.61; 95% confidence interval [CI], −0.07 to 1.29; P=0.053). Mortality at 28 days was 34.5% in the levosimendan group and 30.9% in the placebo group (absolute difference, 3.6 percentage points; 95% CI, −4.5 to 11.7; P=0.43). Among patients requiring ventilation at baseline, those in the levosimendan group were less likely than those in the placebo group to be successfully weaned from mechanical ventilation over the period of 28 days (hazard ratio, 0.77; 95% CI, 0.60 to 0.97; P=0.03). More patients in the levosimendan group than in the placebo group had supraventricular tachyarrhythmia (3.1% vs. 0.4%; absolute difference, 2.7 percentage points; 95% CI, 0.1 to 5.3; P=0.04). 
CONCLUSIONS The addition of levosimendan to standard treatment in adults with sepsis was not associated with less severe organ dysfunction or lower mortality. Levosimendan was associated with a lower likelihood of successful weaning from mechanical ventilation and a higher risk of supraventricular tachyarrhythmia. (Funded by the NIHR Efficacy and Mechanism Evaluation Programme and others; LeoPARDS Current Controlled Trials number, ISRCTN12776039.)

Washout hole for bi-ventricular assist device (BVAD) centrifugal blood pump

The shortage of donor hearts for patients with end stage heart failure has accelerated the development of ventricular assist devices (VAD) that act as a replacement heart. Mechanical devices involving pulsatile, axial and centrifugal devices have been proposed. Recent clinical developments indicate that centrifugal devices are not only beneficial for bridge to transplantation applications, but may also aid myocardial recovery. The results of a recent study have shown that patients who received a VAD have extended lives and improved quality of life compared to recipients of drug therapy. Unfortunately 25% of these patients develop right heart failure syndrome, sepsis and multi-organ failure. It was reported that 17% of patients initially receiving an LVAD later required a right ventricular assist device (RVAD). Hence, current research focus is in the development of a bi-ventricular assist device (BVAD). Current BVAD technology is either too bulky or necessitates having to implant two pumps working independently. The latter requires two different controllers for each pump leading to the potential complication of uneven flow dynamics and the requirements for a large amount of body space. This paper illustrates the combination of the LVAD and RVAD as one complete device to augment the function of both the left and right cardiac chambers with double impellers. The proposed device has two impellers rotating in counter directions, hence eliminating the necessity of the body muscles and tubing/heart connection to restrain the pump. The device will also have two separate chambers with independent rotating impeller for the left and right chambers. A problem with centrifugal impellers is the fluid stagnation underneath the impeller. This leads to thrombosis and blood clots.This paper presents the design, construction and location of washout hole to prevent thrombus for a Bi-VAD centrifugal pump. Results using CFD will be used to illustrate the superiority of our design concept in terms of preventing thrombus formation and hemolysis.

Advances and future directions for management of trauma patients with musculoskeletal injuries

Musculoskeletal injuries are the most common reason for operative procedures in severely injured patients and are major determinants of functional outcomes. In this paper, we summarise advances and future directions for management of multiply injured patients with major musculoskeletal trauma. Improved understanding of fracture healing has created new possibilities for management of particularly challenging problems, such as delayed union and non union of fractures and large bone defects. Optimum timing of major orthopaedic interventions is guided by increased knowledge about the immune response after injury. Individual treatment should be guided by trading off the benefits of early definitive skeletal stabilisation, and the potentially life-threatening risks of systemic complications such as fat embolism, acute lung injury, and multiple organ failure. New methods for measurement of fracture healing and function and quality of life outcomes pave the way for landmark trials that will guide the future management of musculoskeletal injuries.

The hyperthermic patient

Concepts used in this chapter include: Thermoregulation:- Thermoregulation refers to the body’s sophisticated, multi-system regulation of core body temperature. This hierarchical system extends from highly thermo-sensitive neurons in the preoptic region of the brain proximate to the rostral hypothalamus, down to the brain stem and spinal cord. Coupled with receptors in the skin and spine, both central and peripheral information on body temperature is integrated to inform and activate the homeostatic mechanisms which maintain our core temperature at 37oC1. Hyperthermia:- An imbalance between the metabolic and external heat accumulated in the body and the loss of heat from the body2. Exertional heat stroke:- A disorder of excessive heat production coupled with insufficient heat dissipation which occurs in un-acclimated individuals who are engaging in over-exertion in hot and humid conditions. This phenomenon includes central nervous system dysfunction and critical dysfunction to all organ systems including renal, cardiovascular, musculoskeletal and hepatic functions. Non-exertional heat stroke:- In contrast to exertional heatstroke as a consequence of high heat production during strenuous exercise, non-exertional heatstroke results from prolonged exposure to high ambient temperature. The elderly, those with chronic health conditions and children are particularly susceptible.3 Rhabdomylosis:- An acute, sometimes fatal disease characterised by destruction of skeletal muscle. In exertional heat stroke, rhabdomylosis occurs in the context of strenuous exercise when mechanical and/or metabolic stress damages the skeletal muscle, causing elevated serum creatine kinease. Associated with this is the potential development of hyperkalemia, myoglobinuria and renal failure. Malignant hyperthermia:- Malignant hyperthermia is “an inherited subclinical myopathy characterised by a hypermetabolic reaction during anaesthesia. The reaction is related to skeletal muscle calcium dysregulation triggered by volatile inhaled anaesthetics and/or succinylcholine.”4 Presentation includes skeletal muscle rigidity, mixed metabolic and respiratory acidosis, tachycardia, hyperpyrexia, rhabdomylosis, hyperkalaemia, elevated serum creatine kinease, multi-organ failure, disseminated intravascular coagulation and death.5

Dying feet in ICU : why might extracorporeal membrane oxygenation machines cause necrotic feet?

Background Extracorporeal membrane oxygenation (ECMO) is used for severe lung and/or heart failure in intensive care units (ICU). The Prince Charles Hospital (TPCH) has one of the largest ECMO units in Australia. Its use rapidly increased during the H1N1 (“swine flu”) pandemic and an increase in pedal complications resulted. The relationship between ECMO and pedal complications has been described, particularly in children, though no strong data exists. This paper presents a case series of foot complications in patients having received ECMO treatment. Methods We present nine cases of severe foot complications resulting from patients receiving ECMO treatment at TPCH in 2009–2012. Results Case ages ranged from 16 - 58 years and three were male. Six cases had an unremarkable medical history prior to H1N1 or H1N2 infection, one had Cardiomyopathy, one had received a lung transplant, and one had multi-organ failure post-sepsis. Common medications prescribed included vasopressors, antibiotics, and sedatives. All cases showed signs of markedly impaired peripheral perfusion whilst on ECMO and seven developed increasing areas of foot necrosis. Outcomes include two bilateral below knee amputations, two multiple digital amputations, one Reflex Sympathetic Dystrophy Syndrome, three pressure injuries, and three deaths. Conclusion Necrosis of the feet appears to occur more readily in younger people requiring ECMO treatment than others in ICU. The authors are conducting further studies to investigate associations between particular infections, medical history, medications, or machine techniques and severe foot complications. Some of these early results will also be presented at this conference.

Scrub typhus in mainland China, 2006–2012 : the need for targeted public health interventions

Scrub typhus is a vector-borne disease carried by the chigger mite. The aetiological agent is the rickettsia Orientia tsutsugamushi, which is endemic to several countries in the Asia-Pacific region, including China [1]. It is also a travel-associated disease [2] and of great importance among military personnel [3], [4]. During the Second World War, scrub typhus was associated with a higher case fatality ratio than any other infectious disease in the China-Burma-India theatre of operations 1,3. Clinical presentation in patients varies from asymptomatic to life-threatening disease [5], including acute hearing loss and multiple organ failure [6], [7]. To date, there is still no effective and reliable human vaccine against scrub typhus and no point-of-care diagnostics available [1].

Leptospirosis and Leptospires - The silent assassins

Leptospirosis is one of the most common yet under reported zoonoses. Leptospires, the etiological agents of leptospirosis are ubiquitous pathogens, with a world-wide distribution, causing a spectrum of disease ranging from a mild influenza-like illness to Weil’s disease, which manifests itself in multi-organ failure. The following chapter reports on the epidemiology and transmission of the disease in humans and animals. The chapter will also delineate the symptoms observed in humans and animals and in concluding outline unresolved and evolving issues for microbiologists, epidemiologists and public health officials.

Reducing pressure injuries in critically ill patients by using a patient skin integrity care bundle (InSPiRE)

Purpose To test an interventional patient skin integrity bundle, InSPiRE protocol, on the impact of pressure injuries (PrIs) in critically ill patients in an Australian adult intensive care unit (ICU). Methods Before and after design was used where the group of patients receiving the intervention (InSPiRE protocol) was compared with a similar control group who received standard care. Data collected included demographic and clinical variables, skin assessment, PrI presence and stage, and a Sequential Organ Failure Assessment (SOFA) score. Results Overall, 207 patients were enrolled, 105 in the intervention group and 102 in the control group. Most patients were men, mean age 55. The groups were similar on major demographic variables (age, SOFA scores, ICU length of stay). Pressure injury cumulative incidence was significantly lower in the intervention group (18%) compared to the control group for skin injuries(30.4%) (χ2=4.271, df=1, p=0.039) and mucous injuries (t test =3.27, p=<0.001) . Significantly fewer PrIs developing over time in the intervention group (Logrank= 11.842, df=1, p=<0.001) and patients developed fewer skin injuries (>3 PrIs/patient = 1/105) compared with the control group (>3 injuries/patient = 10/102) (p=0.018). Conclusion The intervention group, recieving the InSPiRE protocol, had lower PrI cumulative incidence, and reduced number and severity of PrIs that developed over time. Systematic and ongoing assessment of the patient's skin and PrI risk as well as implementation of tailored prevention measures are central to preventing PrIs.

Determinants of outcome in critically ill patients

Assessment of the outcome of critical illness is complex. Severity scoring systems and organ dysfunction scores are traditional tools in mortality and morbidity prediction in intensive care. Their ability to explain risk of death is impressive for large cohorts of patients, but insufficient for an individual patient. Although events before intensive care unit (ICU) admission are prognostically important, the prediction models utilize data collected at and just after ICU admission. In addition, several biomarkers have been evaluated to predict mortality, but none has proven entirely useful in clinical practice. Therefore, new prognostic markers of critical illness are vital when evaluating the intensive care outcome. The aim of this dissertation was to investigate new measures and biological markers of critical illness and to evaluate their predictive value and association with mortality and disease severity. The impact of delay in emergency department (ED) on intensive care outcome, measured as hospital mortality and health-related quality of life (HRQoL) at 6 months, was assessed in 1537 consecutive patients admitted to medical ICU. Two new biological markers were investigated in two separate patient populations: in 231 ICU patients and 255 patients with severe sepsis or septic shock. Cell-free plasma DNA is a surrogate marker of apoptosis. Its association with disease severity and mortality rate was evaluated in ICU patients. Next, the predictive value of plasma DNA regarding mortality and its association with the degree of organ dysfunction and disease severity was evaluated in severe sepsis or septic shock. Heme oxygenase-1 (HO-1) is a potential regulator of apoptosis. Finally, HO-1 plasma concentrations and HO-1 gene polymorphisms and their association with outcome were evaluated in ICU patients. The length of ED stay was not associated with outcome of intensive care. The hospital mortality rate was significantly lower in patients admitted to the medical ICU from the ED than from the non-ED, and the HRQoL in the critically ill at 6 months was significantly lower than in the age- and sex-matched general population. In the ICU patient population, the maximum plasma DNA concentration measured during the first 96 hours in intensive care correlated significantly with disease severity and degree of organ failure and was independently associated with hospital mortality. In patients with severe sepsis or septic shock, the cell-free plasma DNA concentrations were significantly higher in ICU and hospital nonsurvivors than in survivors and showed a moderate discriminative power regarding ICU mortality. Plasma DNA was an independent predictor for ICU mortality, but not for hospital mortality. The degree of organ dysfunction correlated independently with plasma DNA concentration in severe sepsis and plasma HO-1 concentration in ICU patients. The HO-1 -413T/GT(L)/+99C haplotype was associated with HO-1 plasma levels and frequency of multiple organ dysfunction. Plasma DNA and HO-1 concentrations may support the assessment of outcome or organ failure development in critically ill patients, although their value is limited and requires further evaluation.