Gastrokirurgisen potilaan perioperatiivinen nesteytys - paljon vai vähän, vai siltä väliltä?

Teema : vatsaelinkirurginen potila

Hemodynamics in the critically ill

BACKGROUND Adequate blood circulation is necessary for tissue perfusion and oxygen supply. Derangements in perfusion due to circulatory failure may lead to end-organ failure without prompt and accurate restoration of circulation and perfusion, which is performed by targeting sufficient levels of preload, afterload, and cardiac contractility. Current international guidelines recommend early vigorous fluid resuscitation, restoration of mean arterial pressure (MAP) to ≥60-65 mmHg, when necessary by using vasopressor agents, and restoration of depressed cardiac contractility and output by inotrope treatment to improve survival and avoid end-organ failure. However, evidence for the beneficial impact of inotrope use in septic shock, hemodynamic targets for resuscitation in severe acute pancreatitis (SAP), or optimal blood pressure for prevention of septic acute kidney injury is rather limited. Furthermore, feasible means of assessing fluid responsiveness to prevent excessive fluid resuscitation are warranted. The objective of this study was to evaluate different hemodynamic variables in addition to vasopressor and inotrope treatment during the early phases of severe sepsis, septic shock, and SAP and their association with development of end-organ failure and outcome. We also sought to find relevant hemodynamic parameters for assessing fluid responsiveness during early resuscitation of septic shock. PATIENTS A total of 1022 patients, 440 with septic shock, 159 with SAP, and 423 with severe sepsis, were included in the study. All patients were treated in the ICUs of Helsinki University Hospital during 2005-2012, except for the 423 patients with severe sepsis, who were treated in 13 different Finnish ICUs during 2011-2012. MAIN RESULTS Of patients with septic shock, 44.3% received inotrope treatment during the first 24 hours in the ICU, the majority of these patients receiving dobutamine (90.3%). The mortality of inotrope receivers was significantly higher than that of non-receivers (42.5% vs. 23.9%). Patients who received inotropes were generally more severely ill and received higher doses of norepinephrine. The use of inotropes in these patients was independently associated with worse outcome, also after adjustment with propensity score. In patients with severe sepsis and SAP, the use of inotropes was less frequent, 16.0% and 16.4%, respectively. Vasopressors, most often norepinephrine, were administered to the majority of patients with severe sepsis, SAP, and septic shock. The highest dose of norepinephrine during the first day in ICU was associated with worse outcome. Lower MAP, higher central venous pressure (CVP), and lower cardiac index (CI), but not higher heart rate (HR), were associated with 90-day mortality in patients with SAP. Decreases in MAP and systolic arterial pressure were the best predictors of fluid responsiveness in 20 mechanically ventilated patients with septic shock during a temporary elevation of positive end-expiratory pressure (PEEP) from 10 to 20 cm H2O. A decrease of less than 8% ruled out fluid responsiveness, with a negative predictive value of 100%. The time-adjusted MAP during the first 24 hours in the ICU of patients developing acute kidney injury (AKI) during the first five days in the ICU was significantly lower than that of patients not developing AKI (74.4 mmHg vs. 78.6 mmHg). The best cut-off value for time-adjusted MAP was 72.7 mmHg. Lower time-adjusted MAP or alternatively time-adjusted MAP below 73 mmHg was independently associated with progression of AKI. CONCLUSIONS Inotropes are frequently used in patients with septic shock. In severe sepsis and SAP, inotrope use is less frequent. The vast majority of patients received vasopressor treatment. Norepinephrine was the vasopressor of choice in nearly all patients. Use of inotropes and the highest vasopressor dose during the first day in ICU were significantly associated with 90-day mortality. Although inotropes may have beneficial effects in patients with septic shock, by increasing cardiac output and perfusion, they might also have adverse effects that eventually lead to higher mortality. Although vigorous fluid resuscitation is advocated in the early treatment of SAP to maintain sufficient tissue perfusion, our study showed that overzealous resuscitation might be harmful, reflected by the association of higher CVP with worse outcome. To avoid overhydration during fluid resuscitation of patients with septic shock, a lack of a decrease in MAP during elevation of PEEP from 10 to 20 cm H2O may be used as an accessory means of assessing fluid responsiveness. Lower time-adjusted MAP in patients with severe sepsis is associated with progression of AKI. Higher targets of MAP may be indicated for ensuring adequate perfusion of the kidney in this patient group.  TAUSTAA Riittävä verenkierto ja kudosten perfuusio takaa kudosten hapensaannin. Vakava sairaus, kuten septinen shokki, vakava sepsis tai akuutti haimatulehdus, saattaa häiritä verenkierron olosuhteita niin, että kudosten hapensaanti kärsii. Jatkuessaan tämä voi johtaa elinvaurioihin, kuten akuuttiin munuaisvaurioon. Tehohoidon kulmakiviä on nopea riittävän verenkierron ja perfuusion takaaminen vakavasti sairaille potilaille, jotta pysyvät elinhäiriöt voidaan estää. Verenkiertoa tuetaan nesteytyksellä ja verenpainetta nostavilla, sekä sydämen supistuvuutta (inotroopit) lisäävillä lääkkeillä pyrkien yleisesti hyväksyttyihin verenkierron tavoitearvoihin. Näyttö sydämen supistuvuutta lisäävien lääkkeiden hyödystä septisessä shokissa, vakavan akuutin haimatulehduksen verenkierron optimaalisista tavoitteista, sekä riittävästä keskiverenpainetasosta vakavassa sepsiksessä jotta akuutin munuaisvaurion syntyä voitaisiin estää on puutteellinen. Lisäksi liikanesteytyksen haitoista saadaan lisääntyvästi näyttöä. Menetelmille joilla voidaan arvioida hyötyykö potilas lainkaan lisänesteytyksestä on edelleen tarvetta. Tämän tutkimuksen pyrkimyksenä oli vastata näihin edellä mainittuihin kysymyksiin ja haasteisiin. POTILAAT Tutkimus kattoi 1022 tehohoitopotilasta, joista 440 sairasti septistä shokkia, 423 vakavaa sepsistä ja 159 sairasti vakaavaa akuuttia haimatulehdusta. Tutkimus suoritettiin Helsingin yliopistollisen keskussairaalan teho-osastoilla vuosina 2005-2012, sekä 423 vakavan sepsispotilaan osalta 17 eri teho-osastolle Suomessa vuosina 2011-2012. TULOKSET Septisessä shokissa ensimmäisen vuorokauden aikana inotrooppeja sai 44.3 % (186/420) potilaista, yleensä dobutamiinia (90.3%). Inotrooppia saaneiden potilaiden kuolleisuus oli selvästi muita potilaita korkeampi (42.5% ja 23.9%). Inotrooppien käyttö oli itsenäinen kuolleisuuteen vaikuttava tekijä, myös kun sairauden vakavuusaste ja todennäköisyys saada inotrooppeja huomioitiin. Tehohoitoa saaneilla haimatulehduspotilailla korkea keskuslaskimopaine, matala sydämen minuuttitilavuusindeksi, sekä alhainen keskiverenpaine olivat itsenäisiä kuolleisuuteen vaikuttavia tekijöitä. Keskiverenpaineen ja systolisen verenpaineen lasku nostetun loppu-uloshengityspaineen (PEEP) aikana ennusti parhaiten nestevasteisuutta, eli suotuisaa vastetta lisänesteytykselle septisessä shokissa. Suotuisana vasteena pidettiin 15% lisäystä minuuttitilavuuteen nestetäytön jälkeen. Mikäli PEEP noston yhteydessä tasolta 10 cm H2O tasolle 20 cm H2O potilaan mitattu keskiverenpainetason lasku oli vähemmän kuin 8 %, tämä osoitti varsin selvästi, ettei potilas tulisi hyötymään lisänesteytyksestä (negatiivinen ennustearvo 100%). Vakavassa sepsiksessä aikapainotettu keskiverenpaine ensimmäisen vuorokauden aikana oli selvästi alhaisempi niillä potilailla, jotka kehittivät akuutin munuaisten vajaatoiminnan ensimmäisen viiden tehovuorokauden aikana, kun niillä, jotka eivät munuaisten vajaatoimintaa kehittäneet (74,4 mmHg ja 78.6 mmHg). Keskiverenpaineen paras kynnysarvo akuutin munuaisvaurion kehittymiselle oli 72.7 mmHg. Alhainen keskiverenpaine tai keskiverenpainetaso alle 73 mmHg olivat itsenäisiä munuaisten vajaatoimintaan liittyviä tekijöitä. PÄÄTELMÄ Vaikka sydämen supistuvuutta lisäävillä lääkkeillä on tiettyjä hyödyllisiä vaikutuksia, niillä voi mahdollisesti olla myös haitallisia ja kuolleisuutta lisääviä vaikutuksia. Hyötyjä ja haittoja olisi tarkasti punnittava näiden lääkkeiden käyttöä harkittaessa. Vaikka runsas nesteytys kuuluu vakavan akuutin haimatulehduksen keskeiseen alkuvaiheen hoitoon, saattaa kuitenkin liian runsaalla nesteytyksellä olla haittavaikutuksia, mikä nähdään korkean keskuslaskimopaineen yhteytenä kuolleisuuteen. Jotta liiallinen nesteytys voidaan tehopotilailla välttää, voidaan mahdollisesti PEEPin noston aikaista verenpaineen muutosta käyttää hyväksi. Näyttäisi siltä, että alhainen verenpainetaso vakavassa sepsiksessä on yhteydessä akuutin munuaistenvajaatoiminnan syntyyn. Mahdollisesti olisi syytä harkita nykyisiä suosituksia (yli 60-65 mmHg) korkeampia keskiverenpaineen tavoitearvoja munuaisten toiminnan turvaamiseksi

Verenkiertovajauksen monitorointi ja hoito

Teema : tehohoitolääketiede. English summaryPeer reviewe

Beta-blocker treatment in the critically ill : a systematic review and meta-analysis

Background Critical illness may lead to activation of the sympathetic system. The sympathetic stimulation may be further increased by exogenous catecholamines, such as vasopressors and inotropes. Excessive adrenergic stress has been associated with organ dysfunction and higher mortality. beta-Blockers may reduce the adrenergic burden, but they may also compromise perfusion to vital organs thus worsening organ dysfunction. To assess the effect of treatment with beta-blockers in critically ill adults, we conducted a systematic review and meta-analysis of randomized controlled trials. Materials and methods We conducted a search from three major databases: Ovid Medline, the Cochrane Central Register for Controlled Trials and Scopus database. Two independent reviewers screened, selected, and assessed the included articles according to prespecified eligibility criteria. We assessed risk of bias of eligible articles according to the Cochrane guidelines. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results Sixteen randomized controlled trials comprising 2410 critically ill patients were included in the final review. A meta-analysis of 11 trials including 2103 patients showed a significant reduction in mortality in patients treated with beta-blockers compared to control (risk ratio 0.65, 95%CI 0.53-0.79; p < .0001). There was no significant difference in mean arterial pressure or vasopressor load. Quality of life, biventricular ejection fraction, blood lactate levels, cardiac biomarkers and mitochondrial function could not be included in meta-analysis due to heterogenous reporting of outcomes. Conclusions In this systematic review we found that beta-blocker treatment reduced mortality in critical illness. Use of beta-blockers in critical illness thus appears safe after initial hemodynamic stabilization. High-quality RCT's are needed to answer the questions concerning optimal target group of patients, timing of beta-blocker treatment, choice of beta-blocker, and choice of physiological and hemodynamic parameters to target during beta-blocker treatment in critical illness. KEY MESSAGES A potential outcome benefit of beta-blocker treatment in critical illness exists according to the current review and meta-analysis. Administration of beta-blockers to resuscitated patients in the ICU seems safe in terms of hemodynamic stability and outcome, even during concomitant vasopressor administration. However, further studies, preferably large RCTs on beta-blocker treatment in the critically ill are needed to answer the questions concerning timing and choice of beta-blocker, patient selection, and optimal hemodynamic targets.Peer reviewe

Control groups in recent septic shock trials : a systematic review

The interpretation of septic shock trial data is profoundly affected by patients, control intervention, co-interventions and selected outcome measures. We evaluated the reporting of control groups in recent septic shock trials. We searched for original articles presenting randomized clinical trials (RCTs) in adult septic shock patients from 2006 to 2016. We included RCTs focusing on septic shock patients with at least two parallel groups and at least 50 patients in the control group. We selected and evaluated data items regarding patients, control group characteristics, and mortality outcomes, and calculated a data completeness score to provide an overall view of quality of reporting. A total of 24 RCTs were included (mean n = 287 patients and 71 % of eligible patients were randomized). Of the 24 studies, 14 (58 %) presented baseline data on vasopressors and 58 % the proportion of patients with elevated lactate values. Five studies (21 %) provided data to estimate the proportion of septic shock patients fulfilling the Sepsis-3 definition. The mean data completeness score was 19 out of 36 (range 8-32). Of 18 predefined control group characteristics, a mean of 8 (range 2-17) were reported. Only 2 (8 %) trials provided adequate data to confirm that their control group treatment represented usual care. Recent trials in septic shock provide inadequate data on the control group treatment and hemodynamic values. We propose a standardized trial dataset to be created and validated, comprising characteristics of patient population, interventions administered, hemodynamic values achieved, surrogate organ dysfunction, and mortality outcomes, to allow better analysis and interpretation of future trial results.Peer reviewe

Cerebrovascular autoregulation following cardiac arrest : Protocol for a post hoc analysis of the randomised COMACARE pilot trial

Background Approximately two-thirds of the mortality following out of hospital cardiac arrest is related to devastating neurological injury. Previous small cohort studies have reported an impaired cerebrovascular autoregulation following cardiac arrest, but no studies have assessed the impact of differences in oxygen and carbon dioxide tensions in addition to mean arterial pressure management. Methods This is a protocol and statistical analysis plan to assess the correlation between changes in cerebral tissue oxygenation and arterial pressure as measure of cerebrovascular autoregulation, the tissue oxygenation index, in patients following out of hospital cardiac arrest and in healthy volunteers. The COMACARE study included 120 comatose survivors of out of hospital cardiac arrest admitted to ICU and managed with low-normal or high-normal targets for mean arterial pressure, arterial oxygen and carbon dioxide partial pressures. In addition, 102 healthy volunteers have been investigated as a reference group for the tissue oxygenation index. In both cohorts, the cerebral tissue oxygenation was measured by near infrared spectroscopy. Conclusions Cerebrovascular autoregulation is critical to maintain homoeostatic brain perfusion. This study of changes in autoregulation following out of hospital cardiac arrest over the first 48 hours, as compared to data from healthy volunteers, will generate important physiological information that may guide the rationale and design of interventional studies.Peer reviewe

The Association Between Arterial Oxygen Level and Outcome in Neurocritically Ill Patients is not Affected by Blood Pressure

Background In neurocritically ill patients, one early mechanism behind secondary brain injury is low systemic blood pressure resulting in inadequate cerebral perfusion and consequent hypoxia. Intuitively, higher partial pressures of arterial oxygen (PaO2) could be protective in case of inadequate cerebral circulation related to hemodynamic instability. Study purpose We examined whether the association between PaO2 and mortality is different in patients with low compared to normal and high mean arterial pressure (MAP) in patients after various types of brain injury. Methods We screened the Finnish Intensive Care Consortium database for mechanically ventilated adult (>= 18) brain injury patients treated in several tertiary intensive care units (ICUs) between 2003 and 2013. Admission diagnoses included traumatic brain injury, cardiac arrest, subarachnoid and intracranial hemorrhage, and acute ischemic stroke. The primary exposures of interest were PaO2 (recorded in connection with the lowest measured PaO2/fraction of inspired oxygen ratio) and the lowest MAP, recorded during the first 24 h in the ICU. PaO2 was grouped as follows: hypoxemia ( 18.3 kPa, the highest 10th percentile), and MAP was divided into equally sized tertiles ( 68 mmHg). The primary outcome was 1-year mortality. We tested the association between hyperoxemia, MAP, and mortality with a multivariable logistic regression model, including the PaO2, MAP, and interaction of PaO2*MAP, adjusting for age, admission diagnosis, premorbid physical performance, vasoactive use, intracranial pressure monitoring use, and disease severity. The relationship between predicted 1-year mortality and PaO2 was visualized with locally weighted scatterplot smoothing curves (Loess) for different MAP levels. Results From a total of 8290 patients, 3912 (47%) were dead at 1 year. PaO2 was not an independent predictor of mortality: the odds ratio (OR) for hyperoxemia was 1.16 (95% CI 0.85-1.59) and for hypoxemia 1.24 (95% CI 0.96-1.61) compared to normoxemia. Higher MAP predicted lower mortality: OR for MAP 60-68 mmHg was 0.73 (95% CI 0.64-0.84) and for MAP > 68 mmHg 0.80 (95% CI 0.69-0.92) compared to MAP <60 mmHg. The interaction term PaO2*MAP was nonsignificant. In Loess visualization, the relationship between PaO2 and predicted mortality appeared similar in all MAP tertiles. Conclusions During the first 24 h of ICU treatment in mechanically ventilated brain injured patients, the association between PaO2 and mortality was not different in patients with low compared to normal MAP.Peer reviewe

Lower heart rate is associated with good one-year outcome in post-resuscitation patients

Background: Optimal hemodynamic goals in post-resuscitation patients are not clear. Previous studies have reported an association between lower heart rate and good outcome in patients receiving targeted temperature management (TTM) after out-of-hospital cardiac arrest. Methods: We analyzed heart rate (HR) and outcome data of 504 post-resuscitation patients from the prospectively collected database of the FINNRESUSCI study. One-year neurologic outcome was dichotomized by the Cerebral Performance Category (CPC) to good (1-2) or poor (3-5). Results: Of 504 patients, 40.1% (202/504) had good and 59.9% (302/504) had poor one-year neurologic outcome. Patients with good outcome had lower time-weighted mean HR during the first 48 h in the ICU (69.2 bpm [59.2-75.1] vs. 76.6 bpm [65.72-89.6], p <0.001) and the first 72 h in the ICU (71.2 bpm [65.0-79.0] vs. 77.1 bpm [69.1-90.1, p <0.001]). The percentage of HR registrations below HR threshold values (60, 80 and 100 bpm) were higher for patients with good neurologic outcome, p <0.001 for all. Lower time-weighted HR for 0-48 h and 0-72 h, and a higher percentage of HR recordings below threshold values were independently associated with good neurological one-year outcome (p <0.05 for all). When TTM and non-TTM patients were analyzed separately, HR parameters were independently associated with one-year neurologic outcome only in non-TTM patients. Conclusion: Lower heart rate was independently associated with good neurologic outcome. Whether HR in post-resuscitation patients is a prognostic indicator or an important variable to be targeted by treatment, needs to be assessed in future prospective controlled clinical trials.Peer reviewe

Mean arterial pressure and vasopressor load after out-of-hospital cardiac arrest : Associations with one-year neurologic outcome

The aim of the study: There are limited data on blood pressure targets and vasopressor use following cardiac arrest. We hypothesized that hypotension and high vasopressor load are associated with poor neurological outcome following out-of-hospital cardiac arrest (OHCA). Methods: We included 412 patients with OHCA included in FINNRESUSCI study conducted between 2010 and 2011. Hemodynamic data and vasopressor doses were collected electronically in one, two or five minute intervals. We evaluated thresholds for time-weighted (TW) mean arterial pressure (MAP) and outcome by receiver operating characteristic (ROC) curve analysis, and used multivariable analysis adjusting for co-morbidities, factors at resuscitation, an illness severity score, TW MAP and total vasopressor load (VL) to test associations with one-year neurologic outcome, dichotomized into either good (1-2) or poor (3-5) according to the cerebral performance category scale. Results: Of 412 patients, 169 patients had good and 243 patients had poor one-year outcomes. The lowest MAP during the first six hours was 58 (inter-quartile range [IQR] 56-61) mmHg in those with a poor outcome and 61 (59-63) mmHg in those with a good outcome (p <0.01), and lowest MAP was independently associated with poor outcome (OR 1.02 per mmHg, 95% CI 1.00-1.04, p = 0.03). During the first 48h the median (IQR) of the 1W mean MAP was 80 (78-82) mmHg in patients with poor, and 82 (81-83) mmHg in those with good outcomes (p=0.03) but in multivariable analysis TWA MAP was not associated with outcome. Vasopressor load did not predict one-year neurologic outcome. Conclusions: Hypotension occurring during the first six hours after cardiac arrest is an independent predictor of poor one-year neurologic outcome. High vasopressor load was not associated with poor outcome and further randomized trials are needed to define optimal MAP targets in OHCA patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.Peer reviewe

Near-infrared spectroscopy after out-of-hospital cardiac arrest

BackgroundCerebral hypoperfusion may aggravate neurological damage after cardiac arrest. Near-infrared spectroscopy (NIRS) provides information on cerebral oxygenation but its relevance during post-resuscitation care is undefined. We investigated whether cerebral oxygen saturation (rSO(2)) measured with NIRS correlates with the serum concentration of neuron-specific enolase (NSE), a marker of neurological injury, and with clinical outcome in out-of-hospital cardiac arrest (OHCA) patients.MethodsWe performed a post hoc analysis of a randomised clinical trial (COMACARE, NCT02698917) comparing two different levels of carbon dioxide, oxygen and arterial pressure after resuscitation from OHCA with ventricular fibrillation as the initial rhythm. We measured rSO(2) in 118 OHCA patients with NIRS during the first 36h of intensive care. We determined the NSE concentrations from serum samples at 48h after cardiac arrest and assessed neurological outcome with the Cerebral Performance Category (CPC) scale at 6months. We evaluated the association between rSO(2) and serum NSE concentrations and the association between rSO(2) and good (CPC 1-2) and poor (CPC 3-5) neurological outcome.ResultsThe median (inter-quartile range (IQR)) NSE concentration at 48h was 17.5 (13.4-25.0) g/l in patients with good neurological outcome and 35.2 (22.6-95.8) g/l in those with poor outcome, pPeer reviewe