Miklós Lipcsey

Arterial carbon dioxide tension and outcome in patients admitted to the intensive care unit after cardiac arrest

BACKGROUND Arterial carbon dioxide tension (PaCO2) affects neuronal function and cerebral blood flow. However, its association with outcome in patients admitted to intensive care unit (ICU) after cardiac arrest (CA) has not been evaluated. METHODS AND RESULTS Observational cohort study using data from the Australian New Zealand (ANZ) Intensive Care Society Adult-Patient-Database (ANZICS-APD). Outcomes analyses were adjusted for illness severity, co-morbidities, hypothermia, treatment limitations, age, year of admission, glucose, source of admission, PaO2 and propensity score. We studied 16,542 consecutive patients admitted to 125 ANZ ICUs after CA between 2000 and 2011. Using the APD-PaCO2 (obtained within 24 h of ICU admission), 3010 (18.2%) were classified into the hypo- (PaCO2<35 mmHg), 6705 (40.5%) into the normo- (35-45 mmHg) and 6827 (41.3%) into the hypercapnia (>45 mmHg) group. The hypocapnia group, compared with the normocapnia group, had a trend toward higher in-hospital mortality (OR 1.12 [95% CI 1.00-1.24, p=0.04]), lower rate of discharge home (OR 0.81 [0.70-0.94, p<0.01]) and higher likelihood of fulfilling composite adverse outcome of death and no discharge home (OR 1.23 [1.10-1.37, p<0.001]). In contrast, the hypercapnia group had similar in-hospital mortality (OR 1.06 [0.97-1.15, p=0.19]) but higher rate of discharge home among survivors (OR 1.16 [1.03-1.32, p=0.01]) and similar likelihood of fulfilling the composite outcome (OR 0.97 [0.89-1.06, p=0.52]). Cox-proportional hazards modelling supported these findings. CONCLUSIONS Hypo- and hypercapnia are common after ICU admission post-CA. Compared with normocapnia, hypocapnia was independently associated with worse clinical outcomes and hypercapnia a greater likelihood of discharge home among survivors.

Near infrared spectroscopy (NIRS) of the thenar eminence in anesthesia and intensive care

Near infrared spectroscopy of the thenar eminence (NIRSth) is a noninvasive bedside method for assessing tissue oxygenation. The NIRS probe emits light with several wavelengths in the 700- to 850-nm interval and measures the reflected light mainly from a predefined depth. Complex physical models then allow the measurement of the relative concentrations of oxy and deoxyhemoglobin, and thus tissue saturation (StO2), as well as an approximation of the tissue hemoglobin, given as tissue hemoglobin index.Here we review of current knowledge of the application of NIRSth in anesthesia and intensive care.We performed an analytical and descriptive review of the literature using the terms “near-infrared spectroscopy” combined with “anesthesia,” “anesthesiology,” “intensive care,” “critical care,” “sepsis,” “bleeding,” “hemorrhage,” “surgery,” and “trauma” with particular focus on all NIRS studies involving measurement at the thenar eminence.We found that NIRSth has been applied as clinical research tool to perform both static and dynamic assessment of StO2. Specifically, a vascular occlusion test (VOT) with a pressure cuff can be used to provide a dynamic assessment of the tissue oxygenation response to ischemia. StO2 changes during such induced ischemia-reperfusion yield information on oxygen consumption and microvasculatory reactivity. Some evidence suggests that StO2 during VOT can detect fluid responsiveness during surgery. In hypovolemic shock, StO2 can help to predict outcome, but not in septic shock. In contrast, NIRS parameters during VOT increase the diagnostic and prognostic accuracy in both hypovolemic and septic shock. Minimal data are available on static or dynamic StO2 used to guide therapy.Although the available data are promising, further studies are necessary before NIRSth can become part of routine clinical practice.

Septic acute kidney injury: hemodynamic syndrome, inflammatory disorder, or both?

Septic acute kidney injury (S-AKI) is the most common cause of kidney injury in the ICU. Decreased renal blood flow and inflammation have both been suggested as mechanisms of S-AKI. Benes and colleagues present a study of S-AKI in which sepsis is induced by fecal peritonitis and bacterial infusion. In this study, although decreased renal blood flow and increased renal vascular resistance were present in some of the animals that developed S-AKI, inflammatory activation without decreased renal blood flow and increased renal vascular resistance was seen in other animals. Systemic hemodynamic findings provided little information on renal hemodynamics or risk of S-AKI. The study highlights the extraordinary complexity of S-AKI and the need for clinicians to recognize our limited understanding of its pathogenesis and the weakness of the decreased perfusion paradigm as the sole explanation for the loss of renal function seen in severe sepsis.

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

Abstract 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 (eGFRcystatinC) ≤ 80 mL/min/1.73 m2, 75% had eGFR ≤ 50 mL/min/1.73 m2, and 30% had eGFR ≤ 20 mL/min/1.73 m2. In contrast, only 46% of the patients had reduced renal function assessed by plasma creatinine alone, and only 47% had eGFRMDRD ≤ 80 mL/min/1.73 m2. The mean difference between eGFRMDRD and eGFRcystatinC was 39 mL/min/1.73 m2 for eGFRcystatinC values ≤ 60 mL/min/1.73 m2. Conclusions. GFR is commonly assessed in the ICU. Cystatin C-estimated GFR yields markedly lower GFR results than plasma creatinine and eGFRMDRD. 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.

Endotoxin neutralization and anti-inflammatory effects of tobramycin and ceftazidime in porcine endotoxin shock

IntroductionAntibiotics used for treatment of severe bacterial infections have been shown to exert effects on the inflammatory response in addition to their antibacterial effects. The aim of the present study was to investigate whether the biological effects of endotoxin in a porcine model could be neutralized by tobramycin, and whether tobramycin or ceftazidime was able to modulate the inflammatory response.MethodThirteen piglets were subjected to endotoxin infusion at an initial rate of 4 μg/kg per hour, which was reduced to 1 μg/kg per hour after 30 min. Before endotoxin infusion, the animals received saline (n = 4), ceftazidime (n = 5), or tobramycin (n = 4) at clinically relevant doses. Physiological parameters were measured and blood samples were taken hourly for 6 hours for analysis of tumour necrosis factor-α, IL-6 and endotoxin concentrations.ResultsAll of the animals exhibited physiological signs of severe sepsis without major differences between the groups. Plasma endotoxin concentration was stable after 1 hour. There were no differences in endotoxin concentration or initial tumour necrosis factor-α and IL-6 concentrations between the groups. At 6 hours the IL-6 concentration was significantly lower in the ceftazidime group than in the saline group (P < 0.05), and in both the ceftazidime and the tobramycin groups there were significantly greater reductions from peak values (P < 0.05).ConclusionThere was no neutralization of the biological effects of endotoxin in this porcine model. However, our data indicate a possible anti-inflammatory effect exerted by both ceftazidime and tobramycin, which manifested as a significantly greater reduction in IL-6 in comparison with the untreated group.

Effect of the administration rate on the biological responses to a fixed dose of endotoxin in the anesthetized pig.

There have been difficulties to demonstrate a relationship between endotoxin concentration and clinical response. One hypothesis for this difficulty might be that a fast increase in endotoxin concentration elicits a stronger biological response than a more gradual one of the same dose. The aim of the present study was to investigate the existence of such a response. Eighteen randomized pigs were given the same amount of endotoxin either with an initial infusion rate of 4 &mgr;g kg−1 h−1, which after 1 h was tapered to 0.5 &mgr;g kg−1 h−1, and after 2 h to 0.063 &mgr;g kg−1 h−1 (group I), or with a reverse escalating order with the lowest infusion rate given first (group II). After 3 h, the endotoxin infusion was stopped, and the pigs were observed for another 3 h. The responses in TNF-&agr;, core temperature, leukocytes, platelets, MAP, left ventricular stroke work index, mixed venous saturation, base excess, pH, and pulmonary compliance were greater in group I than in group II, whereas the IL-6 response did not differ between groups. The biological responses of inflammation, hypotension, hypoperfusion, and organ dysfunction are increased if the organism is exposed to a fixed amount of endotoxin more quickly.Abbreviations - BE-Base excess; CI-Cardiac index; DO2-Oxygen delivery; Fio2-fraction of oxygen; Hb-Hemoglobin; LVSWI-Left ventricular stroke work index; MPAP-Mean pulmonary arterial pressure; Paco2-Arterial partial pressure of carbon dioxide; Pao2-Arterial partial pressure of oxygen; pH-Potentia Hydrogenii; SEM-Standard error of the mean; Svo2-Venous oxygen saturation

Effect of a single dose of tobramycin on systemic inflammatory response-induced acute kidney injury in a 6-hour porcine model*

Objective: To evaluate whether the addition of tobramycin further compromises renal function in inflammatory response‐induced acute kidney injury. Effective antibiotic treatment in septic shock is crucial for the outcome. The combination of aminoglycosides with different [beta]‐lactam antibiotics offers a broad antimicrobial coverage, rapid bacterial killing, synergistic effects, and low antibiotic‐induced endotoxin release. However, aminoglycosides have nephrotoxic effects that may aggravate sepsis‐induced acute kidney injury. Design: Prospective, randomized, placebo‐controlled experimental study. Setting: University research unit. Subjects: Twenty‐four healthy pigs. Interventions: The animals were anesthetized and randomized to four groups. Groups I (n = 8) and II (n = 8) received endotoxin infusion for 6 hrs, whereas groups III (n = 4) and IV (n = 4) received saline. Groups I and III received 7 mg/kg of tobramycin 20 mins after the initiation of the protocol, whereas groups II and IV received saline. Measurements and Main Results: The renal elimination rate of a bolus dose of cefuroxime was chosen as the primary end point. Renal function was also evaluated by urine output, creatinine clearance, plasma cystatin C, plasma urea, and urine NAG (N‐acetyl‐beta‐D‐glucoaminidase). After 3 hrs, there were significantly lower cefuroxime elimination rates in the two endotoxin groups than in the nonendotoxin groups. No difference in cefuroxime elimination rates between groups I and II could be detected at any time point. Similarly, there were changes indicating acute kidney injury in urine output, creatinine clearance, and plasma cystatin C in the endotoxin groups with no differences between groups I and II. Plasma urea and urine NAG did not differ between any of the groups. Conclusions: The result of this study does not lend any support to the hypothesis that a single dose of tobramycin enhances the risk of acute renal failure in cases with systemic inflammatory response‐induced acute kidney injury.

Analysis of intraosseous samples using point of care technology—An experimental study in the anaesthetised pig

BACKGROUND Intraosseous access is an essential method in emergency medicine when other forms of vascular access are unavailable and there is an urgent need for fluid or drug therapy. A number of publications have discussed the suitability of using intraosseous access for laboratory testing. We aimed to further evaluate this issue and to study the accuracy and precision of intraosseous measurements. METHODS Five healthy, anaesthetised pigs were instrumented with bilateral tibial intraosseous cannulae and an arterial catheter. Samples were collected hourly for 6h and analysed for blood gases, acid base status, haemoglobin and electrolytes using an I-Stat point of care analyser. RESULTS There was no clinically relevant difference between results from left and right intraosseous sites. The variability of the intraosseous sample values, measured as the coefficient of variance (CV), was maximally 11%, and smaller than for the arterial sample values for all variables except SO2. For most variables, there seems to be some degree of systematic difference between intraosseous and arterial results. However, the direction of this difference seems to be predictable. CONCLUSION Based on our findings in this animal model, cartridge based point of care instruments appear suitable for the analysis of intraosseous samples. The agreement between intraosseous and arterial analysis seems to be good enough for the method to be clinically useful. The precision, quantified in terms of CV, is at least as good for intraosseous as for arterial analysis. There is no clinically important difference between samples from left and right tibia, indicating a good reproducibility.

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 μg endotoxin × kg−1 × h−1 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-α (TNF-α) concentration during the last 3 hours of the experiment. Despite the early reduction of the endotoxin load, no effect on TNF-α 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-α peak or later will have very little or no effect on TNF-α–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.

Slight increase of serum S-100B during porcine endotoxemic shock may indicate blood-brain barrier damage.

Septic shock is a condition that affects many organs, but little is known about the effects on the central nervous system. S-100B, an acidic low molecular weight protein, has attracted considerable interest as a marker for brain damage and disintegration of the blood-brain barrier. It is released into the cerebrospinal fluid and blood from brain tissue after brain damage. We studied S-100B in a porcine model of endotoxemic shock that resembles human Gram-negative septic shock. Ten piglets received IV endotoxin, and plasma samples were collected before the endotoxin infusion and each hour (1–6 h) during the endotoxin infusion. S-100B was measured by sandwich enzyme-linked immunosorbent assay. Low levels of plasma S-100B were detected, but there was a significant increase in S-100B during Hours 1–5 in comparison with the 0 values. We determined that endotoxemia causes a very small but significant increase in the levels of the widely used brain damage marker serum S-100B. However, it cannot be excluded that the increase in S-100B could be caused by release from organs other than the brain.