Continuous chest compressions are associated with higher peak inspiratory pressures when compared to 30:2 in an experimental cardiac arrest model.

BACKGROUND: Ventilation during cardiopulmonary resuscitation (CPR) has long been a part of the standard treatment during cardiac arrests. Ventilation is usually given either during continuous chest compressions (CCC) or during a short pause after every 30 chest compressions (30:2). There is limited knowledge of how ventilation is delivered if it effects the hemodynamics and if it plays a role in the occurrence of lung injuries. The aim of this study was to compare ventilation parameters, hemodynamics, blood gases and lung injuries during experimental CPR given with CCC and 30:2 in a porcine model. METHODS: Sixteen pigs weighing approximately 33 kg were randomized to either receive CPR with CCC or 30:2. Ventricular fibrillation was induced by passing an electrical current through the heart. CPR was started after 3 min and given for 20 min. Chest compressions were provided mechanically with a chest compression device and ventilations were delivered manually with a self-inflating bag and 12 l/min of oxygen. During the experiment, ventilation parameters and hemodynamics were sampled continuously, and arterial blood gases were taken every five minutes. After euthanasia and cessation of CPR, the lungs and heart were removed in block and visually examined followed by sampling of lung tissue which were examined using microscopy. RESULTS: In the CCC group and the 30:2 group, peak inspiratory pressure (PIP) was 58.6 and 35.1 cmH2O (p < 0.001), minute volume (MV) 2189.6 and 1267.1 ml (p < 0.001), peak expired carbon dioxide (PECO2) 28.6 and 39.4 mmHg (p = 0.020), partial pressure of carbon dioxide (PaCO2) 50.2 and 61.1 mmHg (p = 0.013) and pH 7.3 and 7.2 (p = 0.029), respectively. Central venous pressure (CVP) decreased more over time in the 30:2 group (p = 0.023). All lungs were injured, but there were no differences between the groups. CONCLUSIONS: Ventilation during CCC resulted in a higher PIP, MV and pH and lower PECO2 and PaCO2, showing that ventilation mode during CPR can affect ventilation parameters and blood gases.

Increased levels of plasma cytokines and correlations to organ failure and 30-day mortality in critically ill Covid-19 patients.

BACKGROUND: The infection caused by SARS CoV-2 has been postulated to induce a cytokine storm syndrome that results in organ failure and even death in a considerable number of patients. However, the inflammatory response in Corona virus disease-19 (Covid-19) and its potential to cause collateral organ damage has not been fully elucidated to date. This study aims to characterize the acute cytokine response in a cohort of critically ill Covid-19 patients. METHOD: 24 adults with PCR-confirmed Covid-19 were included at time of admission to intensive care a median of eleven days after initial symptoms. Eleven adult patients admitted for elective abdominal surgery with preoperative plasma samples served as controls. All patients were included after informed consent was obtained. 27 cytokines were quantified in plasma. The expression of inflammatory mediators was then related to routine inflammatory markers, SAPS3, SOFA score, organ failure and 30-day mortality. RESULTS: A general increase in cytokine expression was observed in all Covid-19 patients. A strong correlation between respiratory failure and IL-1ra, IL-4, IL-6, IL-8 and IP-10 expression was observed. Acute kidney injury development correlated well with increased levels of IL-1ra, IL-6, IL-8, IL-17a, IP-10 and MCP-1. Generally, the cohort demonstrated weaker correlations between cytokine expression and 30-day mortality out of which IL-8 showed the strongest signal in terms of mortality. CONCLUSION: The present study found that respiratory failure, acute kidney injury and 30-day mortality in critically ill Covid-19 patients are associated with moderate increases of a broad range of inflammatory mediators at time of admission.

A non-fatal intoxication and seven deaths involving the dissociative drug 3-MeO-PCP.

INTRODUCTION: 3-methoxyphencyclidine (3-MeO-PCP) appeared on the illicit drug market in 2011 and is an analogue of phencyclidine, which exhibits anesthetic, analgesic and hallucinogenic properties. In this paper, we report data from a non-fatal intoxication and seven deaths involving 3-MeO-PCP in Sweden during the period March 2014 until June 2016. CASE DESCRIPTIONS: The non-fatal intoxication case, a 19-year-old male with drug problems and a medical history of depression, was found awake but tachycardic, hypertensive, tachypnoeic and catatonic at home. After being hospitalized, his condition worsened as he developed a fever and lactic acidosis concomitant with psychomotor agitation and hallucinations. After 22h of intensive care, the patient had made a complete recovery. During his hospitalization, a total of four blood samples were collected at different time points. The seven autopsy cases, six males and one female, were all in their twenties to thirties with psychiatric problems and/or an ongoing drug abuse. METHODS: 3-MeO-PCP was identified with liquid chromatography (LC)/time-of-flight technology and quantified using LC-tandem mass spectrometry. RESULTS: In the clinical case, the concentration of 3-MeO-PCP was 0.14µg/g at admission, 0.08µg/g 2.5h after admission, 0.06µg/g 5h after admission and 0.04µg/g 17h after admission. The half-life of 3-MeO-PCP was estimated to 11h. In the autopsy cases, femoral blood concentrations ranged from 0.05µg/g to 0.38µg/g. 3-MeO-PCP was the sole finding in the case with the highest concentration and the cause of death was established as intoxication with 3-MeO-PCP. In the remaining six autopsy cases, other medications and drugs of abuse were present as well. CONCLUSION: Despite being scheduled in January 2015, 3-MeO-PCP continues to be abused in Sweden. Exposure to 3-MeO-PCP may cause severe adverse events and even death, especially if the user does not receive life-supporting treatment.

Identification of tissue-specific cell death using methylation patterns of circulating DNA.

Minimally invasive detection of cell death could prove an invaluable resource in many physiologic and pathologic situations. Cell-free circulating DNA (cfDNA) released from dying cells is emerging as a diagnostic tool for monitoring cancer dynamics and graft failure. However, existing methods rely on differences in DNA sequences in source tissues, so that cell death cannot be identified in tissues with a normal genome. We developed a method of detecting tissue-specific cell death in humans based on tissue-specific methylation patterns in cfDNA. We interrogated tissue-specific methylome databases to identify cell type-specific DNA methylation signatures and developed a method to detect these signatures in mixed DNA samples. We isolated cfDNA from plasma or serum of donors, treated the cfDNA with bisulfite, PCR-amplified the cfDNA, and sequenced it to quantify cfDNA carrying the methylation markers of the cell type of interest. Pancreatic ß-cell DNA was identified in the circulation of patients with recently diagnosed type-1 diabetes and islet-graft recipients; oligodendrocyte DNA was identified in patients with relapsing multiple sclerosis; neuronal/glial DNA was identified in patients after traumatic brain injury or cardiac arrest; and exocrine pancreas DNA was identified in patients with pancreatic cancer or pancreatitis. This proof-of-concept study demonstrates that the tissue origins of cfDNA and thus the rate of death of specific cell types can be determined in humans. The approach can be adapted to identify cfDNA derived from any cell type in the body, offering a minimally invasive window for diagnosing and monitoring a broad spectrum of human pathologies as well as providing a better understanding of normal tissue dynamics.

Pulmonary influences on early post-operative recovery in patients after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy treatment: a retrospective study.

BACKGROUND: The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a curative treatment option for peritoneal carcinomatosis (PC). There have been few studies on the pulmonary adverse events (AEs) affecting patient recovery after this treatment, thus this study investigated these factors. METHODS: Between January 2005 and December 2006, clinical data on all pulmonary AEs and the recovery progress were reviewed for 76 patients with after CRS and HIPEC. Patients with pulmonary interventions (thoracocenthesis and chest tubes) were compared with the non-intervention patients. Two senior radiologists, blinded to the post-operative clinical course, separately graded the occurrence of pulmonary AEs. RESULTS: Of the 76 patients, 6 had needed thoracocentesis and another 6 needed chest tubes. There were no differences in post-operative recovery between the intervention and non-intervention groups. The total number of days on mechanical ventilation, the length of stay in the intensive care unit, total length of hospital stay, tumor burden, and an American Society of Anesthesiologists (ASA) grade of greater than 2 were correlated with the occurrence of atelectasis and pleural effusion. Extensive atelectasis (grade 3 or higher) was seen in six patients, major pleural effusion (grade 3) in seven patients, and signs of heart failure (grade 1-2) in nine patients. CONCLUSIONS: Clinical and radiological post-operative pulmonary AEs are common after CRS and HIPEC. However, most of the pulmonary AEs did not affect post-operative recovery.

Hypoxia due to cardiac arrest induces a time-dependent increase in serum amyloid ß levels in humans.

Amyloid ß (Aß) peptides are proteolytic products from amyloid precursor protein (APP) and are thought to play a role in Alzheimer disease (AD) pathogenesis. While much is known about molecular mechanisms underlying cerebral Aß accumulation in familial AD, less is known about the cause(s) of brain amyloidosis in sporadic disease. Animal and postmortem studies suggest that Aß secretion can be up-regulated in response to hypoxia. We employed a new technology (Single Molecule Arrays, SiMoA) capable of ultrasensitive protein measurements and developed a novel assay to look for changes in serum Aß42 concentration in 25 resuscitated patients with severe hypoxia due to cardiac arrest. After a lag period of 10 or more hours, very clear serum Aß42 elevations were observed in all patients. Elevations ranged from approximately 80% to over 70-fold, with most elevations in the range of 3-10-fold (average approximately 7-fold). The magnitude of the increase correlated with clinical outcome. These data provide the first direct evidence in living humans that ischemia acutely increases Aß levels in blood. The results point to the possibility that hypoxia may play a role in the amyloidogenic process of AD.

Significant differences when using creatinine, modification of diet in renal disease, or cystatin C for estimating glomerular filtration rate in ICU patients.

BACKGROUND: Renal dysfunction is associated with increased morbidity and mortality in intensive care patients. In most cases the glomerular filtration rate (GFR) is estimated based on serum creatinine and the Modification of Diet in Renal Disease (MDRD) formula, but cystatin C-estimated GFR is being used increasingly. The aim of this study was to compare creatinine and MDRD and cystatin C-estimated GFR in intensive care patients. METHODS: Retrospective observational study was performed, on patients treated within the general intensive care unit (ICU) during 2004-2006, in a Swedish university hospital. RESULTS: GFR markers are frequently ordered in the ICU; 92% of the patient test results had cystatin C-estimated GFR (eGFR(cystatinC)) ≤ 80 mL/min/1.73 m(2), 75% had eGFR ≤ 50 mL/min/1.73 m(2), and 30% had eGFR ≤ 20 mL/min/1.73 m(2). In contrast, only 46% of the patients had reduced renal function assessed by plasma creatinine alone, and only 47% had eGFR(MDRD) ≤ 80 mL/min/1.73 m(2). The mean difference between eGFR(MDRD) and eGFR(cystatinC) was 39 mL/min/1.73 m(2) for eGFR(cystatinC) values ≤ 60 mL/min/1.73 m(2). CONCLUSIONS: GFR is commonly assessed in the ICU. Cystatin C-estimated GFR yields markedly lower GFR results than plasma creatinine and eGFR(MDRD). Many pharmaceuticals are eliminated by the kidney, and their dosage is adjusted for kidney function. Thus, the differences in GFR estimates by the methods used indicate that the GFR method used in the intensive care unit may influence the treatment.

Inflammatory and circulatory effects of the reduction of endotoxin concentration in established porcine endotoxemic shock--a model of endotoxin elimination.

OBJECTIVE: To study whether a reduction of the endotoxin load, once a generalized inflammatory state has been established, reduces the inflammatory response and endotoxin-induced effects on circulation, hypoperfusion, and organ dysfunction. DESIGN: Prospective parallel-grouped placebo-controlled randomized interventional experimental study. SETTING: University research unit. SUBJECTS: Healthy pigs. INTERVENTIONS: The animals were subjected to a continuous endotoxin infusion rate of either 4.0 or 0.063 microg endotoxin x kg x h for 1, 2, or 6 hours. The 1- and 2-hour infusion groups represented the applied therapy by a reduction of the endotoxin load of 5/6 and 2/3, respectively. MEASUREMENTS AND MAIN RESULTS: During a 6-hour experiment, laboratory and physiologic parameters were recorded hourly in 26 anesthetized and mechanically ventilated pigs. Primary end point was to detect differences in tumor necrosis factor-alpha (TNF-alpha) concentration during the last 3 hours of the experiment. Despite the early reduction of the endotoxin load, no effect on TNF-alpha concentration was observed. Similarly, in circulatory parameters, such as mean arterial pressure and oxygen delivery, and in platelet count and renal function, no effects were noted. However, there was some improvement in pulmonary compliance and function as determined by Pao2, Paco2, and pH. These changes were associated with slight improvements in leukocyte response and capillary leakage. CONCLUSIONS: Termination of the endotoxin infusion represents an incontestable model of endotoxin concentration reduction. Endotoxin elimination strategies applied at the TNF-alpha peak or later will have very little or no effect on TNF-alpha-mediated toxicity. Nevertheless, there was an effect on the leukocyte response that was associated with an improvement in respiratory function and microcirculation, making it impossible to rule out fully the beneficial effect of this strategy. However, the effects were limited in relation to the magnitude of the endotoxin concentration reduction and the very early application of the antiendotoxin measure.

Laparoscopic left lobe liver resection in a porcine model: a study of the efficacy and safety of different surgical techniques.

INTRODUCTION: Laparoscopic liver surgery is evolving and the best technique for dividing the liver parenchyma is currently under debate. The aim of this study was to study different techniques during a full laparoscopic lobe resection, and determine the efficacy and risks of bleeding and gas embolism. METHODS: Sixteen pigs were randomized to two groups: group US underwent an operation with Ultracision shears (AutoSonix) and ultrasonic dissector (CUSA) and group VS with a vessel sealing system (Ligasure) and ultrasonic dissector. A left lobe resection was performed. Transesophageal endoscopic echocardiography (TEE) was used to detect gas emboli in the right side of the heart and pulmonary artery. The operations and TEE were recorded for later assessment. RESULTS: Compared with group VS, group US exhibited significantly more intraoperative bleeding (p = 0.02), a trend towards a longer operation time (p = 0.08), and a trend towards more embolization for grade I emboli. In total, 10 of 15 animals had emboli during the operation. CONCLUSIONS: This study showed that a laparoscopic left lobe resection can be performed with a combination of AutoSonix and CUSA as well as with Ligasure and CUSA instrumentation. In our hands, less bleeding was incurred with Ligasure than with AutoSonix.