Hemodynamic and metabolic recovery in acute myocardial infarction-related cardiogenic shock is more rapid among patients presenting with out-of-hospital cardiac arrest.

BACKGROUND: Most studies in acute myocardial infarction complicated by cardiogenic shock (AMICS) include patients presenting with and without out-of-hospital cardiac arrest (OHCA). The aim was to compare OHCA and non-OHCA AMICS patients in terms of hemodynamics, management in the intensive care unit (ICU) and outcome. METHODS: From a cohort corresponding to two thirds of the Danish population, all patients with AMICS admitted from 2010-2017 were individually identified through patient records. RESULTS: A total of 1716 AMICS patients were identified of which 723 (42%) presented with OHCA. A total of 1532 patients survived to ICU admission. At the time of ICU arrival, there were no differences between OHCA and non-OHCA AMICS patients in variables commonly used in the AMICS definition (mean arterial pressure (MAP) (72mmHg vs 70mmHg, p = 0.12), lactate (4.3mmol/L vs 4.0mmol/L, p = 0.09) and cardiac output (CO) (4.6L/min vs 4.4L/min, p = 0.30)) were observed. However, during the initial days of ICU treatment OHCA patients had a higher MAP despite a lower need for vasoactive drugs, higher CO, SVO2 and lactate clearance compared to non-OHCA patients (p<0.05 for all). In multivariable analysis outcome was similar but cause of death differed significantly with hypoxic brain injury being leading cause in OHCA and cardiac failure in non-OHCA AMICS patients. CONCLUSION: OHCA and non-OHCA AMICS patients initially have comparable metabolic and hemodynamic profiles, but marked differences develop between the groups during the first days of ICU treatment. Thus, pooling of OHCA and non-OHCA patients as one clinical entity in studies should be done with caution.

Activation of the Nitric Oxide Pathway and Acute Myocardial Infarction Complicated by Acute Kidney Injury.

BACKGROUND/AIMS: The pathophysiology of acute kidney injury (AKI) in ST-elevation myocardial infarction (STEMI) patients remains poorly explored. The involvement of the nitric oxide (NO) pathway has been demonstrated in experimental ischemic AKI. The aim of this study was to assess the predictive value of circulating biomarkers of the NO pathway for AKI in STEMI patients. METHODS: Four hundred and twenty-seven STEMI patients treated with primary percutaneous coronary intervention were included. The primary end point was AKI. Biomarkers of the NO pathway (plasma superoxide dismutase [SOD], uric acid, nitrite/nitrate [NOx], neopterin) as well as cardiac biomarkers (B-type natriuretic peptide [BNP] and troponin) were sampled 12 h after admission. The predictive value of circulating biomarkers was evaluated in addition to the multivariate clinical model. RESULTS: AKI developed in 8.9% of patients. The 3-month mortality was significantly higher in patients with AKI (34.2 vs. 4.1%; p < 0.001). SOD, uric acid, NOx, neopterin, BNP and troponin were significantly associated with the development of AKI (area under curve [AUC]-receiver operating curve [ROC] ranging between 0.70 and 0.81). In multivariate analysis cardiogenic shock, neopterin, NOx and troponin were independent predictors of AKI. AUC-ROC of the association of multibiomarkers and clinical model was 0.90 and outperformed the predictive value of the clinical model alone. OR of NOx ≥45 µmol/L was 8.0 (95% CI 3.1-20.6) for AKI. CONCLUSION: Biomarkers of the NO pathway are associated with the development of AKI in STEMI patients. These results provide insights into the pathophysiology of AKI and may serve at developing preventing strategies for AKI targeting this pathway.

Serum Lactate and A Relative Change in Lactate as Predictors of Mortality in Patients With Cardiogenic Shock - Results from the Cardshock Study.

INTRODUCTION: Cardiogenic shock complicating acute myocardial infarction has a very high mortality. Our present study focuses on serial measurement of lactate during admission due to cardiogenic shock and the prognostic effect of lactate and a relative change in lactate in patients after admission and the institution of intensive care treatment. METHODS AND RESULTS: This is a secondary analysis of the CardShock study. Data on lactate at baseline were available on 217 of 219 patients.In the study population, the median baseline lactate was 2.8 mmol/L (min-max range, 0.5-23.1 mmol/L).At admission, lactate was predictive of 30-day mortality with an adjusted Hazard ratio (HR) of 1.20 mmol/L (95% confidence interval, CI 1.14-1.27). Within the first 24 h of admission, baseline lactate remained predictive of 30-day mortality. Lactate at 6 h had a HR of 1.14 (95% CI 1.06-1.24) and corresponding values at 12 and 24 h had a HR of 1.10 (1.04-1.17), and of HR 1.19 (95% CI 1.07-1.32), respectively. A 50% reduction in lactate within 6 h resulted in a HR of 0.82 (95% CI 0.72-0.94). Corresponding hazard ratios at 12 and 24 h, were 0.87 (95% CI 0.76-0.98) and 0.74 (95% CI 0.60-0.91), respectively. CONCLUSION: The main findings of the present study are that baseline lactate is a powerful predictor of 30-day mortality, lactate at 6, 12, and 24 h after admission are predictors of 30-day mortality, and a relative change in lactate is a significant predictor of survival within the first 24 h after instituting intensive care treatment adding information beyond the information from baseline values.

Adenosine Plasma Level and A2A Receptor Expression in Patients With Cardiogenic Shock.

OBJECTIVES: To investigate whether adenosine A2A receptors lead to vasodilation and positive inotropic function under stimulation and whether they play a role in the control of blood pressure in patients with cardiogenic shock. DESIGN: Prospective observational study. SETTING: Monocentric, Hopital Nord, Marseille, France. SUBJECTS: Patients with cardiogenic shock (n = 16), acute heart failure (n = 16), and acute myocardial infarction (n = 16). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Arterial adenosine plasma level and A2A receptor expression on peripheral blood mononuclear cells were evaluated by mass spectrometry and Western blot, respectively, at admission and after 24 hours. Hemodynamic parameters, including systemic vascular resistance, were also assessed. Mean adenosine plasma level at admission was significantly higher in patients with cardiogenic shock (2.74 ± 1.03 µM) versus acute heart failure (1.33 ± 0.27) or acute myocardial infarction (1.19 ± 0.27) (normal range, 0.4-0.8 µM) (p < 0.0001). No significant correlation was found between adenosine plasma level and systemic vascular resistance. Mean adenosine plasma level decreased significantly by 24 hours after admission in patients with cardiogenic shock (2.74 ± 1.03 to 1.53 ± 0.68; p < 0.001). Mean A2A receptor expression was significantly lower in patients with cardiogenic shock (1.18 ± 0.11) versus acute heart failure (1.18 ± 0.11 vs 1.39 ± 0.08) (p = 0.005). CONCLUSIONS: We observed high adenosine plasma level and low A2A receptor expression at admission in patients with cardiogenic shock versus acute heart failure or acute myocardial infarction. This may contribute to the physiopathology of cardiogenic shock.

Lactate in cardiogenic shock - current understanding and clinical implications.

Adenosine triphosphate (ATP) is an essential substrate metabolite in human beings. Mitochondrial oxidative phosphorylation provides > 95% of ATP with the remainder derived from glycolysis or tricarboxylic acid cycle (TCA). In normal hearts, acetyl-CoA is synthesized from the ß-oxidation of free fatty acids (FFA) and the oxidation of pyruvate. Pyruvate is synthesized from glycolysis and can be submitted either for decarboxylation to acetyl-CoA or for dehydrogenation to lactate. Moreover, pyruvate, as well as lactate, plays a key role in aerobic glucose metabolism which is highly dependent on ubiquitous regulatory mechanisms. Many recent advances in molecular biology, genetics, and physiology have revealed new insights into the metabolic flux of lactate. The initial perception characterized by increased lactate production and accumulation in peripheral tissues in anaerobic conditions has been recently contested. The paradigm of increased lactate concentration in the anaerobic setting is discussed according to contemporary reports. Nevertheless, the clinical role of lactate as a prognostic factor in cardiovascular diseases is undisturbed, especially in the field of innovative technology of left/bi ventricular-assist devices and biochips where it reassured its diagnostic and prognostic impact on the cardiovascular system.

Suppressed MMP-9 Activity in Myocardial Infarction-Related Cardiogenic Shock Implies Diminished Rage Degradation.

BACKGROUND: Receptor for advanced glycation end products (RAGE) and its cleavage fragment soluble RAGE (sRAGE) are opposite players in inflammation. Enhanced monocytic RAGE expression and decreased plasma sRAGE levels are associated with higher mortality in infarction-related cardiogenic shock. Active matrix metalloproteinase-9 (MMP-9) has been implied in RAGE ectodomain cleavage and subsequently sRAGE shedding in vitro. We investigated MMP-9 activity in myocardial infarction-induced cardiogenic shock with regard to RAGE/sRAGE regulation. METHODS AND RESULTS: We determined MMP-9 serum activity by zymography and tissue inhibitor of matrix metalloproteinases (TIMP-1) expression by Western blot and correlated it to RAGE/sRAGE data in patients with cardiogenic shock after acute myocardial infarction (CS, n = 30), in patients with acute myocardial infarction without shock (AMI, n = 20) and in healthy volunteers (n = 20).MMP-9 activity is increased in AMI (P = 0.02 versus controls), but significantly decreased in CS with lowest levels in non-survivors (n = 13, P = 0.02 versus AMI). In all patients, MMP-9 activity correlated inversely with RAGE expression on circulating monocytes (r = -0.57; P = 0.0001; n = 50).TIMP-1 levels showed an inverse regulation in comparison to active MMP-9 with significantly decreased levels in AMI as compared with controls (P = 0.02 versus controls) and highest levels in non-survivors of CS (P <0.001 versus AMI). CONCLUSIONS: Serum MMP-9 activity is increased in acute myocardial infarction, but markedly suppressed in cardiogenic shock. Maintaining MMP-9 activity could be a therapeutic target to limit RAGE-induced deleterious inflammation in cardiogenic shock.

Percutaneous left atrial decompression in adults with refractory cardiogenic shock supported with veno-arterial extracorporeal membrane oxygenation.

BACKGROUND AND AIM OF THE STUDY: Left ventricular (LV) distention, a recognized complication in patients supported with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock, can lead to pulmonary edema, increased myocardial oxygen consumption, and LV thrombus formation. Atrial septostomy was examined as a management strategy for LV distension. METHODS: Of 72 patients supported with VA-ECMO, seven patients underwent atrial septostomy through a trans-septal approach. The primary indication for atrial septostomy was refractory pulmonary edema. RESULTS: The mean time from ECMO initiation to LA decompression was 1.3 days (range 0-2 days). There was a 100% procedural success rate with improvement in pulmonary edema. Five patients survived to discharge with one patient exhibiting recovery of biventricular function, two patients were transplanted, one patient was decannulated, and one patient was transitioned to long-term durable ventricular assist device. Two patients died, one from multi-organ failure and one with severe anoxic brain injury. CONCLUSION: Atrial septostomy is an effective method of LV decompression that can be performed safely with a high success rate.

Prognostic implications of fluid balance in ST elevation myocardial infarction complicated by cardiogenic shock.

BACKGROUND: Positive fluid balance has been associated with adverse outcomes in patients admitted to general intensive care units. We analysed the relationship between a positive fluid balance and its persistence over time in terms of in-hospital outcomes among ST elevation myocardial infarction (STEMI) patients complicated by cardiogenic shock. METHODS: We retrospectively studied fluid intake and output for 96 hours following hospital admission in 48 consecutive adult patients with STEMI complicated by cardiogenic shock, all undergoing primary angioplasty. Daily and accumulated fluid balance was registered at up to 96 hours following admission. The cohort was stratified into two groups based on the presence or absence of positive fluid balance on day 4. Patients' records were assessed for in-hospital adverse outcomes, as well as 30-day all-cause mortality. RESULTS: A positive fluid balance was present in 19/48 patients (40%). Patients with positive fluid balance were older and more likely to be treated by intra-aortic balloon counter-pulsation and antibiotics. These patients were more likely to develop acute kidney injury and to need new intubation and were less likely to have renal function recovery as well as successful weaning from mechanical ventilation ( p < 0.05 for all). Patients with positive fluid balance had higher 30-day mortality (68% vs. 10%; p < 0.001). In a multivariate Cox regression model, for every 1-L increase in positive fluid balance, the adjusted risk for 30-day mortality increased by 24% (hazard ratio: 1.24, 95% confidence interval: 1.07-1.42; p = 0.003). CONCLUSIONS: A positive fluid balance was strongly associated with higher 30-day mortality in STEMI complicated by cardiogenic shock.

Infectious Complications and Immune/Inflammatory Response in Cardiogenic Shock Patients: A Prospective Observational Study.

INTRODUCTION: Patients with cardiogenic shock (CS) are at a high risk of developing infectious complications; however, their early detection is difficult, mainly due to a frequently occurring noninfectious inflammatory response, which accompanies an extensive myocardial infarction (MI) or a postcardiac arrest syndrome. The goal of our prospective study was to describe infectious complications in CS and the immune/inflammatory response based on a serial measurement of several blood-based inflammatory biomarkers. METHODS: Eighty patients with CS were evaluated and their infections were monitored. Inflammatory markers (C-reactive protein, procalcitonin, pentraxin 3, presepsin) were measured seven times per week. The control groups consisted of 11 patients with ST segment elevation myocardial infarction without CS and without infection, and 22 patients in septic shock. RESULTS: Infection was diagnosed in 46.3% of patients with CS; 16 patients developed an infection within 48 h. Respiratory infection was most common, occurring in 33 out of 37 patients. Infection was a significant or even the main reason of death only in 3.8% of all patients with CS, and we did not find statistically significant difference in 3-month mortality between group of patients with CS with and without infection. There was no statistically significant prolongation of the duration of mechanical ventilation associated with infection. Strong inflammatory response is often in patients with CS due to MI, but we found no significant difference in the course of the inflammatory response expressed by evaluated biomarkers in patients with CS with and without infection. We found a strong relationship between the elevated inflammatory markers (sampled at 12 h) and the 3-month mortality: the area under the curve of receiver operating characteristic ranged between 0.683 and 0.875. CONCLUSION: The prevalence of infection in patients with CS was 46.3%, and respiratory tract infections were the most common type. Infections did not prolong statistically significantly the duration of mechanical ventilation and did not increase the prevalence of hospital mortality in this high-risk CS population. CS due to acute myocardial infarction was accompanied by a strong and highly variable inflammatory response, but it did not reach the intensity of the inflammatory response observed in patients with septic shock. An extensive immune/inflammatory response in patients with CS is linked to a poor prognosis.

Extracorporeal Membrane Oxygenation as a Bridge for Heart Failure and Cardiogenic Shock.

Heart failure (HF) can be defined as cardiac structural or functional abnormality leading to a series of symptoms due to deficiency of oxygen delivery. In the clinical practice, acute heart failure (AHF) is usually performed as cardiogenic shock (CS), pulmonary edema, and single or double ventricle congestive heart failure. CS refers to depressed or insufficient cardiac output (CO) attributable to myocardial infarction, fulminant myocarditis, acute circulatory failure attributable to intractable arrhythmias or the exacerbation of chronic heart failure, postcardiotomy low CO syndrome, and so forth. Epidemiological studies have shown that CS has higher in-hospital mortality in patients with AHF. Besides, we call the induced, sustained circulatory failure even after administration of high doses of inotropes and vasopressors refractory cardiogenic shock. In handling these cases, mechanical circulatory support devices are usually needed. In this review, we discuss the current application status and clinical points in utilizing extracorporeal membrane oxygenation (ECMO).

Platelet mitochondrial dysfunction in critically ill patients: comparison between sepsis and cardiogenic shock.

INTRODUCTION: Platelet mitochondrial respiratory chain enzymes (that produce energy) are variably inhibited during human sepsis. Whether these changes occur even during other acute critical illness or are associated with impaired platelet aggregation and secretion (that consume energy) is not known. The aims of this study were firstly to compare platelet mitochondrial respiratory chain enzymes activity between patients with sepsis and those with cardiogenic shock, and secondly to study the relationship between platelet mitochondrial respiratory chain enzymes activity and platelet responsiveness to (exogenous) agonists in patients with sepsis. METHODS: This was a prospective, observational, case-control study. Platelets were isolated from venous blood of 16 patients with severe sepsis or septic shock (free from antiplatelet drugs) and 16 others with cardiogenic shock, within 48 hours from admission to Intensive Care. Platelet mitochondrial respiratory chain enzymes activity was measured with spectrophotometry and expressed relative to citrate synthase activity, a marker of mitochondrial density. Platelet aggregation and secretion in response to adenosine di-phosphate (ADP), collagen, U46619 and thrombin receptor activating peptide were measured with lumiaggregometry only in patients with sepsis. In total, 16 healthy volunteers acted as controls for both spectrophotometry and lumiaggregometry. RESULTS: Platelets of patients with sepsis or cardiogenic shock similarly had lower mitochondrial nicotinamide adenine dinucleotide dehydrogenase (NADH) (P < 0.001), complex I (P = 0.006), complex I and III (P < 0.001) and complex IV (P < 0.001) activity than those of controls. Platelets of patients with sepsis were generally hypo-responsive to exogenous agonists, both in terms of maximal aggregation (P < 0.001) and secretion (P < 0.05). Lower mitochondrial NADH (R (2) 0.36; P < 0.001), complex I (R (2) 0.38; P < 0.001), complex I and III (R (2) 0.27; P = 0.002) and complex IV (R (2) 0.43; P < 0.001) activity was associated with lower first wave of aggregation with ADP. CONCLUSIONS: Several platelet mitochondrial respiratory chain enzymes are similarly inhibited during human sepsis and cardiogenic shock. In patients with sepsis, mitochondrial dysfunction is associated with general platelet hypo-responsiveness to exogenous agonists. TRIAL REGISTRATION: ClinicalTrials.gov NCT00541827 . Registered 8 October 2007.

Terapias ventilatorias en el manejo del edema agudo de pulmón cardiogénico / Moreno-Zabaleta, R

El edema agudo de pulmón (EAP), fundamentalmente de origen cardiogénico, supone una importante carga asistencial en las urgencias hospitalarias, así como una importante causa de muerte. Junto a un tratamiento médico óptimo, muchas guías recomiendan el uso de CPAP o ventilación mecánica no invasiva. Aunque los meta-análisis publicados hasta ahora muestran suficiente evidencia para recomendar el uso de dispositivos ventilatorios en el edema agudo de pulmón, existe un ensayo clínico que incluye cerca de 1.000 pacientes en el que no se mostró una clara ventaja de la CPAP o la ventilación mecánica no invasiva con respecto a la oxigenoterapia en el tratamiento de estos pacientes. Esto ha generado cierta controversia en el manejo del edema agudo de pulmón con terapias ventilatorias. Como alternativa existen otros dispositivos no mecánicos, como la CPAP de Boussignac o el oxígeno con alto flujo humidificado, que en estudios iniciales parecen tener resultados similares a la CPAP o la ventilación mecánica no invasiva

Acute pulmonary edema (APE), fundamentally of cardiogenic origin, entails a significant care load in the hospital emergency services and is an important cause of death. Together with optimal medical treatment, many guidelines recommend the use of continuous positive airway pressure (CPAP) or non-invasive mechanical ventilation. Although the meta-analyses published up to date show sufficient evidence to recommend the use of ventilatory devices in acute pulmonary edema, there is a clinical trial including approximately 1000 patients in which no clear advantage of the CPAP or non-invasive mechanical ventilation over oxygen therapy in the treatment of these patients was demonstrated. This has generated some controversy regarding the management of acute pulmonary edema with ventilatory therapies. As an alternative, there are other non-mechanical devices such as Boussignac CPAP or high flow humidified oxygen therapy whose results seem to be similar to CPAP or non-invasive mechanical ventilation in the initial studies

Impairment of the endothelial glycocalyx in cardiogenic shock and its prognostic relevance.

In cardiogenic shock (CS), pathophysiological changes include microcirculatory dysfunction, vascular leakage, and an increase in platelet and leukocyte adhesion to the endothelium, as well as endothelial activation and dysfunction. The endothelial glycocalyx has been recognized as a central modulator of these processes. Glycosaminoglycan heparan sulfate is a major component of the glycocalyx of endothelial cells, and syndecan-1 (S1) represents the most prevalent proteoglycan. The aim of the current study was to investigate circulating levels of the glycocalyx components in patients with infarct-related CS. In 184 patients with CS complicating acute myocardial infarction, blood samples were collected at admission and after one day. Intra-aortic balloon pumping was used in 94 patients (51%). Glycosaminoglycan heparan sulfate and S1 were measured using standard enzyme-linked immunosorbent assay kits. All-cause mortality at 30 days was used for outcome assessment. Levels of S1 decreased between days 1 and 2 (339 [interquartile range [QR], 109-852] vs. 220 [IQR, 57-606] ng/mL; P = 0.01). In contrast, glycosaminoglycan heparan sulfate increased over time (1.9 [IQR, 0.3-6.4] vs. 7.1 [IQR, 3.7-11.7] mg/mL; P < 0.001). Survivors at 30 days had lower admission S1 levels (P < 0.001). In multivariable analysis, S1 remained an independent predictor of 30-day mortality (odds ratio per µg/mL, 2.2 [95% confidence interval, 1.30-3.58]; P = 0.003) together with serum lactate, age, and ejection fraction. Increased levels of S1 are an independent predictor of short-term mortality in patients with acute myocardial infarction and CS.ClinicalTrials.gov Identifier: NCT00491036.

Do interleukin-10 and superoxide ions predict outcomes of cardiac extracorporeal membrane oxygenation patients?

Extracorporeal membrane oxygenation (ECMO) is used for cardiogenic shock rescue. It is hard to predict the outcome from this treatment by clinical observation in days soon after installation. We analyzed the plasma levels of interleukin (IL)-6, IL-8, IL-10, reactive oxygen species, and 8-OHdG, and the glutathione peroxidase activities from 23 cases at the time of ECMO installation before resuscitation. Generalized additive models (GAM) were performed to identify the death ranges of every variable, and the variables were further discretized. The impaired release of IL-10 on shock led to death. IL-10 levels at >16.58 pg/ml differentiated death from survival for acute myocardial infarction (AMI) patients, and levels at >143.17 pg/ml did the same for dilated cardiomyopathy (DCMP) patients. The prediction power of discretized IL-10 alone was measured as area under the curve (AUC) 0.913. The generalized linear model was then performed to predict the best composition from both the original and discretized variables and resulted in AUC 0.97 for the combined discretized IL-10 and superoxide ions. Two missed myocarditis cases from IL-10 prediction were resolved by superoxide ion levels. Our observations lead to the hypothesis that a proper response to cardiogenic shock by releasing the appropriate amount of IL-10 is required for survival in the cases of AMI and DCMP. For myocarditis, proper responses in IL-10 and superoxide ions are needed.

Methylene blue for distributive shock: a potential new use of an old antidote.

Methylene blue is used primarily in the treatment of patients with methemoglobinemia. Most recently, methylene blue has been used as a treatment for refractory distributive shock from a variety of causes such as sepsis and anaphylaxis. Many studies suggest that the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway plays a significant role in the pathophysiology of distributive shock. There are some experimental and clinical experiences with the use of methylene blue as a selective inhibitor of the NO-cGMP pathway. Methylene blue may play a role in the treatment of distributive shock when standard treatment fails.

A blinded, randomized, controlled trial of three doses of high-dose insulin in poison-induced cardiogenic shock.

BACKGROUND: High dose insulin (HDI) has proven superior to glucagon and catecholamines in the treatment of poison-induced cardiogenic shock (PICS) in previous animal studies. Standard recommendations for dosing of insulin vary and the optimal dose of HDI in PICS has not been established. Our hypothesis was a dose of 10 U/kg/hr of HDI would be superior to 1 U/kg/hr with cardiac output (CO) as our primary outcome measure in pigs with propranolol-induced PICS. METHODS: This was a blinded, prospective, randomized trial with 4 arms consisting of 4 pigs in each arm. The arms were as follows: placebo (P), 1 U/kg/hr (HDI-1), 5 U/kg/hr (HDI-5), and 10 U/kg/hr (HDI-10). Cardiogenic shock was induced with a bolus of 0.5 mg/kg of propranolol followed by an infusion of 0.25 mg/kg/min until the point of toxicity, defined as 0.75 x (HR x MAP) was reached. At this point the propranolol infusion was decreased to 0.125 mg/kg/min and a 20 mL/kg bolus of normal saline (NS) was administered. The protocol was continued for 6 hours or until the animals died. RESULTS: 2 pigs died in the P arm, 1 pig died each in the HDI-1 and HDI-5 arms, and all pigs lived in the HDI-10 arm. There was a statistically significant difference in dose by time interaction on CO of 1.13 L/min over the 6 hr study period (p = < 0.001). There was also a statistically significant difference in dose by time interaction on MAP, HR, and systemic vascular resistance (SVR). No statistically significant difference was found between any of the arms regarding glucose utilization. CONCLUSION: HDI was statistically and clinically significantly superior to placebo in this propranolol model of PICS. Furthermore a dose response over time was found where CO increased corresponding to increases in doses of HDI.

Interrelationship between blood and tissue lactate in a general intensive care unit: a subcutaneous adipose tissue microdialysis study on 162 critically ill patients.

PURPOSE: The aim of the study was to study the interrelationship between blood and tissue lactate in critically ill patients with or without shock admitted in a general intensive care unit. MATERIALS AND METHODS: We studied 162 mechanically ventilated patients: 106 with shock (septic shock, 97; cardiogenic shock, 9) and 56 without shock (severe sepsis, 38; systemic inflammatory response syndrome, 18). A microdialysis catheter was inserted in the subcutaneous adipose tissue of the upper thigh, and interstitial fluid was collected every 4 hours for a maximum of 6 days. We assessed the relationship between tissue and blood lactate using cross-approximate entropy and cross-correlation analysis. RESULTS: Patients with shock had higher area under the curve for blood (261 vs 175 mmol/L*hours, P < .0001) and tissue lactate (386 vs 281 mmol/L*hours, P < .0001) compared with patients without shock. The interrelationship of tissue-blood lactate, as assessed with cross-approximate entropy, was more regular in patients with shock compared with patients without shock. Cross-correlation of tissue vs blood lactate yielded higher correlation coefficients in patients with shock compared with those without shock, being higher when tissue lactate preceded blood lactate by 4 hours compared with tissue vs blood lactate with no lag time. CONCLUSIONS: In critical illness, the detailed dynamics between blood and tissue lactate are affected by the presence of shock. In patients with shock, microdialysis-assessed tissue lactate is higher compared with those without shock and may detect metabolic disturbances before these become evident in the systemic circulation.

Oxygen transport and mitochondrial function in porcine septic shock, cardiogenic shock, and hypoxaemia.

INTRODUCTION: The relevance of tissue oxygenation in the pathogenesis of organ dysfunction during sepsis is controversial. We compared oxygen transport, lactate metabolism, and mitochondrial function in pigs with septic shock, cardiogenic shock, or hypoxic hypoxia. METHODS: Thirty-two anaesthetized, ventilated pigs were randomized to faecal peritonitis (P), cardiac tamponade (CT), hypoxic hypoxia (HH) or controls. Systemic and regional blood flows, lactate, mitochondrial respiration, and tissue hypoxia-inducible factor 1 alpha (HIF-1α) were measured for 24 h. RESULTS: Mortality was 50% in each intervention group. While systemic oxygen consumption (VO(2) ) was maintained in all groups, hepatic VO(2) tended to decrease in CT [0.84 (0.5-1.3) vs. 0.42 (0.06-0.8)/ml/min/kg; P = 0.06]. In P, fractional hepatic, celiac trunk, and portal vein blood flows, and especially renal blood flow [by 46 (14-91)%; P = 0.001] decreased. In CT, renal blood flow [by 50.4 (23-81)%; P = 0.004] and in HH, superior mesenteric blood flow decreased [by 38.9 (16-100)%, P = 0.009]. Hepatic lactate influx increased > 100% in P and HH, and > 200% in CT (all P < 0.02). Hepatic lactate uptake remained unchanged in P and HH and converted to release in CT. Mitochondrial respiration remained normal. Muscle adenosine triphosphate (ATP) concentrations decreased in P (5.9 ± 1.4 µmol/g wt vs. 2.8 ± 2.7 µmol/g wt, P = 0.04). HIF-1α expression was not detectable in any group. CONCLUSION: We conclude that despite shock and renal hypoperfusion, tissue hypoxia is not a major pathophysiological issue in early and established faecal peritonitis. The reasons for reduced skeletal muscle tissue ATP levels in the presence of well-preserved in-vitro muscle mitochondrial respiration should be further investigated.