Ville Pettilä

Helsinki University Central Hospital | HUCH · Department Anesthesiology, Intensive Care, Emergency Medicine and Pain Medicine

Purpose To assess the association between cystatin C-derived estimates of kidney function and mortality and acute kidney injury (AKI) in sepsis. Materials and methods Post-hoc analysis of sepsis patients in the FINNAKI-cohort (n = 802). Primary outcome was 90-day mortality. We measured plasma cystatin C and creatinine at intensive care unit (ICU)...

Background Fluid bolus therapy is a common intervention to improve urine output. Data concerning the effect of a fluid bolus on oliguria originate mainly from observational studies and remain controversial regarding the actual benefit of such therapy. We compared the effect of a follow-up approach without fluid bolus to a 500 mL fluid bolus on urin...

PurposeTo assess whether pre-existing chronic kidney disease (CKD) modified the relationship between the strategy for renal-replacement theraphy (RRT) initiation and clinical outcomes in the STARRT-AKI trial.Methods This was a secondary analysis of a multi-national randomized trial. We included patients who had documented pre-existing estimated glo...

b> Introduction: Red blood cell (RBC) transfusion may affect the recipient immune system. During RBC storage in an unphysiological environment, RBC quality and function are impaired, the cells bleb extracellular vesicles (EVs), and other bioactive substances accumulate in the storage medium. EVs can carry reactive biomolecules and mediate cell-cell...

Background Timing of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney i...

Importance: In cardiac surgery, albumin solution may maintain hemodynamics better than crystalloids and reduce the decrease in platelet count and excessive fluid balance, but randomized trials are needed to compare the effectiveness of these approaches in reducing surgical complications. Objective: To assess whether 4% albumin solution compared...

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. β-Blockers may reduce the adrenergic burden, but they may als...

Background: Intravenous fluids are recommended for the treatment of patients who are in septic shock, but higher fluid volumes have been associated with harm in patients who are in the intensive care unit (ICU). Methods: In this international, randomized trial, we assigned patients with septic shock in the ICU who had received at least 1 liter o...

Aim We compared the prognostic abilities of neurofilament light (NfL) and neuron-specific enolase (NSE) in patients resuscitated from out-of-hospital cardiac arrest (OHCA) of various aetiologies. Methods We analysed frozen blood samples obtained at 24 and 48 hours from OHCA patients treated in 21 Finnish intensive care units in 2010 and 2011. We d...

Objective: Prognostic models are key for benchmarking intensive care units (ICUs). They require up-to-date predictors and should report transportability properties for reliable predictions. We developed and validated an in-hospital mortality risk prediction model to facilitate benchmarking, quality assurance, and health economics evaluation. Stud...

A post-hoc laboratory study of FINNRESUSCI study: comparison of Neurofilament light (NfL) and Neuron specific enolase (NSE) in prognostication after out-of-hospital cardiac arrest.

Background. Sedation of intensive care patients is needed for patient safety, but deep sedation is associated with adverse outcomes. Frontal electromyogram-based Responsiveness Index (RI) aims to quantify the level of sedation and is scaled 0–100 (low index indicates deep sedation). We compared RI-based sedation to Richmond Agitation-Sedation Scale...

PurposeIntensive care patients have increased risk of death and their care is expensive. We investigated whether risk-adjusted mortality and resources used to achieve survivors change over time and if their variation is associated with variables related to intensive care unit (ICU) organization and structure.Methods Data of 207,131 patients treated...

Background: Prognostic models are key for quality and performance evaluations of intensive care units (ICUs). Lack of temporal and geographical transportability challenges the validity of prognostic models serving as monitoring and benchmarking tools for ICUs.Objective: To develop and validate an in-hospital mortality risk prediction model to facil...

PurposeWe compared a restrictive fluid management strategy to usual care among critically ill patients with acute kidney injury (AKI) who had received initial fluid resuscitation.Methods This multicenter feasibility trial randomized 100 AKI patients 1:1 in seven ICUs in Europe and Australia. Restrictive fluid management included targeting negative...

Background: Acute Kidney Injury (AKI) is often diagnosed based on plasma creatinine (Cr) only. Adjustment of Cr for cumulative fluid balance due to potential dilution of Cr and subsequently missed Cr-based diagnosis of AKI has been suggested, albeit the physiological rationale for these adjustments is questionable. Furthermore, whether these adjus...

Purpose Whether positive fluid balance among patients with acute kidney injury (AKI) stems from decreased urine output, overzealous fluid administration, or both is poorly characterized. Materials and methods This was a post hoc analysis of the prospective multicenter observational Finnish Acute Kidney Injury study including 824 AKI and 1162 non-A...

Background The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. Methods We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensiv...

Despite having a similar post-operative complication profile, cardiac valve operations are associated with a higher mortality rate compared to coronary artery bypass grafting (CABG) operations. For long-term mortality, few predictors are known. In this study, we applied an ensemble machine learning (ML) algorithm to 88 routinely collected peri-oper...

We hypothesised that plasma concentrations of biomarkers of neutrophil activation and pro-inflammatory cytokines differ according to the phase of rapidly evolving sepsis. In an observational study, we measured heparin-binding protein (HBP), myeloperoxidase (MPO), IL-6 and IL-8 in 167 sepsis patients on intensive care unit admission. We prospectivel...

Fibroblast growth factor (FGF) 21 is a marker associated with mitochondrial and cellular stress. Cardiac arrest causes mitochondrial stress, and we tested if FGF 21 would reflect the severity of hypoxia-reperfusion injury after cardiac arrest. We measured serum concentrations of FGF 21 in 112 patients on ICU admission and 24, 48 and 72 h after out-...

Abstract Background Acute kidney injury (AKI) is a frequently occurring syndrome in critically ill patients and is associated with worse outcomes. Biomarkers allow early identification and therapy of AKI which may improve outcomes. Urine chitinase 3-like protein 1 (uCHI3L1) was recently identified as a promising urinary biomarker for AKI. In this m...

Background: Acute kidney injury (AKI) is a frequent and clinically relevant problem in critically ill patients. Various randomized controlled trials (RCT) have attempted to assess potentially beneficial treatments for AKI. Different approaches to applying the Kidney Disease Improving Global Outcomes (KDIGO) criteria for AKI make a comparison of st...

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is released from kidney tubular cells under stress as well as from neutrophils during inflammation. It has been suggested as a biomarker for acute kidney injury (AKI) in critically ill patients with sepsis. To evaluate clinical usefulness of urine NGAL (uNGAL), we post-hoc applied recen...

Background Data on the causes of death and long‐term mortality of intensive care unit‐treated hospital survivors with acute kidney injury (AKI) are limited. The goal of this study was to analyze the causes of death among critically ill patients during a 5‐year follow‐up. Methods In this predetermined sub‐study of a prospective, observational, mult...

To the Editor: In their article on the results of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial, Bagshaw et al. (July 16 issue)¹ report that the accelerated initiation of dialysis, as compared with a standard strategy, resulted in similar mortality among patients with acute kidney...

Introduction: Standard subcutaneous low-molecular-weight heparin (LMWH) thromboprophylaxis yields low anti-factor Xa activity in patients in the intensive care unit (ICU). The aim of the study was to assess coagulation status in ICU patients randomized to receive enoxaparin thromboprophylaxis either as a standard subcutaneous bolus (SCB) or contin...

PurposeNeurofilament light (NfL) is a biomarker reflecting neurodegeneration and acute neuronal injury, and an increase is found following hypoxic brain damage. We assessed the ability of plasma NfL to predict outcome in comatose patients after out-of-hospital cardiac arrest (OHCA). We also compared plasma NfL concentrations between patients treate...

Background In patients with shock after acute myocardial infarction (AMI), the optimal level of pharmacologic support is unknown. Whereas higher doses may increase myocardial oxygen consumption and induce arrhythmias, diastolic hypotension may reduce coronary perfusion and increase infarct size. Objectives This study aimed to determine the optimal...

Background Acute kidney injury is common in critically ill patients, many of whom receive renal-replacement therapy. However, the most effective timing for the initiation of such therapy remains uncertain. Methods We conducted a multinational, randomized, controlled trial involving critically ill patients with severe acute kidney injury. Patients...

Background Oliguria is a frequent trigger for administering a fluid bolus, but the effect of fluid bolus in improving urine output is inadequately demonstrated. Here, we summarize the protocol and detailed statistical analysis plan of the randomized, controlled RESPONSE trial comparing follow‐up as the experimental group and a 500 mL crystalloid fl...

Background: The pathophysiology of septic acute kidney injury is inadequately understood. Recently, subphenotypes for sepsis and AKI have been derived. The objective of this study was to assess whether a combination of comorbidities, baseline clinical data, and biomarkers could classify meaningful subphenotypes in septic AKI with different outcome...

Background: In cardiac surgery with cardiopulmonary bypass (CPB), large amounts of fluids are administered. CPB priming with crystalloid solution causes marked hemodilution and fluid extravasation. Colloid solutions may reduce fluid overload because they have a better volume expansion effect than crystalloids. The European Medicines Agency does no...

Background Circulatory shock affects every third patient in intensive care units and is associated with high mortality. Near-infrared spectroscopy (NIRS) could serve as a means for monitoring tissue perfusion in circulatory shock. Purpose To assess the evidence of NIRS monitoring in circulatory shock, we conducted a systematic review of the litera...

Importance Acute respiratory distress syndrome (ARDS) is associated with high mortality. Interferon (IFN) β-1a may prevent the underlying event of vascular leakage. Objective To determine the efficacy and adverse events of IFN-β-1a in patients with moderate to severe ARDS. Design, Setting, and Participants Multicenter, randomized, double-blind, p...

Background: Fluid accumulation frequently coexists with acute kidney injury (AKI) and is associated with increased risk for AKI progression and mortality. Among septic shock patients, restricted use of resuscitation fluid has been reported to reduce the risk of worsening of AKI. Restrictive fluid therapy, however, has not been studied in the setti...

Objectives: The number of critical care survivors is growing, but their long-term outcomes and resource use are poorly characterized. Estimating the cost-utility of critical care is necessary to ensure reasonable use of resources. The objective of this study was to analyze the long-term resource use and costs, and to estimate the cost-utility, of...

Background: Mortality rates associated with acute kidney injury (AKI) vary among critically ill patients. Outcomes are often not corrected for severity or duration of AKI. Our objective was to analyse whether a new variable, AKI burden, would outperform 1) presence of AKI, 2) highest AKI stage, or 3) AKI duration in predicting 90-day mortality. M...

Activation of intracellular signaling pathways in circulating leukocytes represents an early step in systemic immune-inflammatory response occurring e.g. in acute pancreatitis (AP) and sepsis. Previously, we found aberrations in the phosphorylation of leukocyte signaling proteins in patients with sepsis or AP (measured <48 h from hospital admission...

Background: Mortality prediction models are applied in the Intensive Care Unit (ICU) to stratify patients into different risk categories and to facilitate benchmarking. To ensure that the correct prediction models are applied for these purposes, the best performing models must be identified. As a first step, we aimed to establish a systematic revi...

Background: Acute kidney injury (AKI) occurs in up to 50% of all critically ill patients and hemodynamic abnormalities are assumed to contribute, but their nature and share is still unclear. We explored the associations between hemodynamic variables, including cardiac index and right ventricular function, and the occurrence of AKI in critically il...

Abstract Background Injury to endothelium and glycocalyx predisposes to vascular leak, which may subsequently lead to increased fluid requirements and worse outcomes. In this post hoc study of the prospective multicenter observational Finnish Acute Kidney Injury (FINNAKI) cohort study conducted in 17 Finnish intensive care units, we studied the ass...

Background: In patients with septic shock mortality is high, and survivors experience long-term physical, mental and social impairments. The ongoing Conservative vs Liberal Approach to fluid therapy of Septic Shock in Intensive Care (CLASSIC) trial assesses the benefits and harms of a restrictive versus (vs) standard-care intravenous (IV) fluid th...

Introduction: The optimal level of blood pressure after out-of-hospital cardiac arrest (OHCA) is unknown. Hypotension may aggravate cerebral hypoperfusion exacerbating the post-anoxic brain injury. On the other hand, excessive vasopressor support may increase myocardial oxygen consumption and induce arrhythmias. We aimed to evaluate the effects of...

Background Major surgery predisposes to endothelial qlycocalyx (EG) injury. EG injury associates with cardiac morbidity, including spontaneous myocardial infarction. However, the relation between EG injury and the development of perioperative myocardial infarction (PMI) remains unknown. Methods Fifteen PMI patients and 60 propensity-matched control...

Background: Inflammation, reflected by high plasma interleukin-6 concentration, is associated with acute kidney injury (AKI) in septic patients. Neutrophil activation has pathophysiological significance in experimental septic AKI. We hypothesised that neutrophil activation is associated with AKI in critically ill sepsis patients. Methods: We mea...

Introduction: Intravenous (IV) fluid is a key intervention in the management of septic shock. The benefits and harms of lower versus higher fluid volumes are unknown and clinical equipoise exists. We describe the protocol and detailed statistical analysis plan for the Conservative versus Liberal Approach to fluid therapy of Septic Shock in the Int...

Objectives: Caregivers use clinical examination to timely recognize deterioration of a patient, yet data on the prognostic value of clinical examination are inconsistent. In the Simple Intensive Care Studies-I, we evaluated the association of clinical examination findings with 90-day mortality in critically ill patients. Design: Prospective sing...

Acute kidney injury (AKI) is a syndrome that frequently affects the critically ill. Recently, an increased number of dinucleotide repeats in the HMOX1 gene were reported to associate with development of AKI in cardiac surgery. We aimed to test the replicability of this finding in a Finnish cohort of critically ill septic patients. This multicenter...

The EPO-TBI multi-national randomized controlled trial found that erythropoietin (EPO), when compared to placebo, did not affect 6-month neurological outcome, but reduced illness severity-adjusted mortality in patients with traumatic brain injury (TBI), making the cost-effectiveness of EPO in TBI uncertain. The current study uses patient-level data...

Background: Acute kidney injury (AKI) is common after heart surgery. Neutrophil gelatinase-associated lipocalin (NGAL) is produced in injured kidney. NGAL has been used as an early plasma biomarker for AKI in patients undergoing heart surgery. Neutrophils contain all isoforms (25-kDa, 45-kDa and 145-kDa) but the kidney produces almost exclusively...

Importance Previous research suggested that soluble human recombinant thrombomodulin may reduce mortality among patients with sepsis-associated coagulopathy. Objective To determine the effect of human recombinant thrombomodulin vs placebo on 28-day all-cause mortality among patients with sepsis-associated coagulopathy. Design, Setting, and Partic...

Abstract Background: Cerebral 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 (rSO2) measured with NIRS correlates with the serum conce...

Background: Circulating SN (secretoneurin) concentrations are increased in patients with myocardial dysfunction and predict poor outcome. Because SN inhibits CaMKIIδ (Ca2+/calmodulin-dependent protein kinase IIδ) activity, we hypothesized that upregulation of SN in patients protects against cardiomyocyte mechanisms of arrhythmia. Methods: Circul...

Aim of the study: We evaluated the impact of patient age and time from collapse to return of spontaneous circulation (ROSC) on the prognostic accuracy of neuron specific enolase (NSE) after out-of-hospital cardiac arrest (OHCA). Methods: Using electrochemiluminescence immunoassay, we measured serum concentrations of NSE in 249 patients who were...

Acute kidney injury (AKI) is a syndrome with high incidence among the critically ill. Because the clinical variables and currently used biomarkers have failed to predict the individual susceptibility to AKI, candidate gene variants for the trait have been studied. Studies about genetic predisposition to AKI have been mainly underpowered and of mode...

Objectives: Secretoneurin is associated with cardiomyocyte Ca handling and improves risk prediction in patients with acute myocardial dysfunction. Whether secretoneurin improves risk assessment on top of established cardiac biomarkers and European System for Cardiac Operative Risk Evaluation II in patients undergoing cardiac surgery is not known....

Objectives The current trends in RBC use and pre‐ and post‐transfusion Hb levels were analysed to improve practice and to provide international comparison. Background Indications for RBC transfusion have changed with growing scientific evidence. The lowest acceptable haemoglobin (Hb) level has decreased, and transfusing single units instead of pai...

Purpose We aimed to determine the feasibility of targeting low-normal or high-normal mean arterial pressure (MAP) after out-of-hospital cardiac arrest (OHCA) and its effect on markers of neurological injury. Methods In the Carbon dioxide, Oxygen and Mean arterial pressure After Cardiac Arrest and REsuscitation (COMACARE) trial, we used a 2³ factor...

Purpose We assessed the effects of targeting low-normal or high-normal arterial carbon dioxide tension (PaCO2) and normoxia or moderate hyperoxia after out-of-hospital cardiac arrest (OHCA) on markers of cerebral and cardiac injury. Methods Using a 2³ factorial design, we randomly assigned 123 patients resuscitated from OHCA to low-normal (4.5–4.7...

Introduction: Fibroblast growth factor (FGF) 21 is a novel marker of mitochondrial and cellular stress. Due to the pivotal role of mitochondria in oxidative metabolism and oxidative stress we tested the hypothesis that FGF 21 would reflect the severity of hypoxia-reperfusion injury after cardiac arrest. Methods: We measured serum concentration of F...

Haemodynamic instability predisposes patients to cardiac complications in non-cardiac surgery. Esmolol, a short-acting cardioselective beta-adrenergic blocker might be efficient in perioperative cardiac protection, but could affect other vital organs, such as the kidneys, and post-discharge survival. We performed a systematic review on the use of e...

Purpose: We assessed the association between the premorbid functional status (PFS) and 1-year mortality and functional status of very old intensive care patients. Methods: Using a nationwide quality registry, we retrieved data on patients treated in Finnish intensive care units (ICUs) during the period May 2012‒April 2013. Of 16,389 patients, 18...

Background Studies reporting renal and overall survival after acute kidney injury (AKI) treated exclusively with intermittent modalities of renal replacement therapy (IRRT) are rare. This study focused on outcomes of AKI patients treated with IRRT both in intensive care units (ICUs) and non‐ICU dialysis units. Methods This prospective observationa...

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-resuscitati...

Background: Data on long-term functional outcome and quality of life (QoL) after out-of-hospital cardiac arrest (OHCA) are limited. We assessed long-term functional outcome and health-related QoL of OHCA survivors regardless of arrest aetiology. Methods: All adult unconscious OHCA patients treated in 21 Finnish ICUs between March 2010 and Februa...