Tero Varpula

Early signs of critical illness polyneuropathy in ICU patients with systemic inflammatory response syndrome or sepsis

Abstract Objective: To evaluate with electromyography the incidence and the time of appearance of neuromuscular abnormality in patients with systemic inflammatory response syndrome (SIRS) and/or sepsis. Design: Follow-up study. Setting: Intensive care unit of Helsinki University Hospital, Finland. Patients: Nine mechanically ventilated patients with SIRS and/or sepsis. Interventions: Electromyography and conduction velocity measurements on the 2nd–5th day after admission to the intensive care unit. Measurements and results: In all nine patients electromyography revealed signs of neuromuscular abnormality. The means of compound muscle action potential amplitudes of the median and ulnar nerves were decreased. Fibrillation was observed in four patients out of nine. Conclusion: Because neuromuscular abnormalities seem to develop earlier than previously reported, electroneuromyography should be used more frequently as a diagnostic test.

Predictive power of serum NSE and OHCA score regarding 6-month neurologic outcome after out-of-hospital ventricular fibrillation and therapeutic hypothermia

AIM OF THE STUDY To determine the predictive power of the out-of-hospital cardiac arrest (OHCA) score and serum neuron-specific enolase (NSE) in patients resuscitated from ventricular fibrillation treated with therapeutic hypothermia (TH) and glucose control. METHODS An analysis of prospectively collected data of 90 TH patients. Serum NSE was measured at 24 and 48 h. Outcome was measured by neurologic exam 6 months after cardiac arrest with good outcome defined as a Cerebral Performance Category (CPC) of 1 or 2. RESULTS In multiple logistic regression analysis, age (odds ratio [OR], 95% confidence interval 1.1 [1.03-1.18]/year), NSE at 48 h (OR 1.1 [1.02-1.26]/microg/l), and increase in NSE levels (OR 7.2 [1.7-31.3]) were predictors of poor outcome, but the OHCA score was not. Cut-off points with 100% specificity in predicting poor outcome were 33microg/l for NSE at 48h (sensitivity 43% [28-60%]) and 6.4microg/l for delta NSE 24-48 h (sensitivity 44% [28-60%]). CONCLUSION Increase in NSE between 24 and 48h and NSE at 48h is specific but only moderately sensitive markers of 6-month outcome. Outcome prediction at ICU admission using the OHCA score was not possible in this selected patient population.

Long-term outcome and quality-adjusted life years after severe sepsis

Objective: To study long-term mortality, quality of life (QOL), quality-adjusted life years (QALYs), and costs per QALY in an unselected intensive care unit (ICU) patient population with severe sepsis. Design: Prospective observational cohort study. Setting: Twenty-four ICUs in Finland. Patients: A total of 470 adult patients with severe sepsis who were treated in ICUs between November 1, 2004 and February 28, 2005. The QOL before critical illness was assessed in 252 patients and QOL after severe sepsis in 156 patients (58% of the patients surviving in April 30, 2006). Ninety-eight patients responded to both questionnaires. QOL was assessed by a generic EuroQol-5D (EQ-5D) measurement with summary index (EQsum) and visual analogue scale (VAS). Measurements and Main Results: The 2-year mortality after severe sepsis was 44.9% (211 of 470). The median response time for QOL assessment after severe sepsis was 17 months (interquartile range [IQR] 16–18). The median EQsum (75, IQR 56–92) and EQ VAS (66, IQR 50–80) were lower after severe sepsis than age- and sex-adjusted reference values (p < 0.001 and p < 0.001). The decrease between the mean EQsum reference value and that of severe sepsis patients was 12 (95% confidence interval [CI], 9–16). The difference between the mean EQ VAS reference values and the mean EQ VAS was 8 (95% CI, 5–11). The mean calculated QALYs after severe sepsis were 10.9 (95% CI, 9.7–12.1) and the calculated cost for one QALY was only 2139 &OV0556; for all survivors and nonsurvivors. Conclusions: Two-year mortality after severe sepsis was high (44.9%) and the QOL was lower after severe sepsis than before critical illness as assessed by EQ-5D. However, the mean QALYs for the surviving patients were reasonable and the cost for one QALY was reasonably low, which makes intensive care in patients with severe sepsis cost effective.

Airway pressure release ventilation as a primary ventilatory mode in acute respiratory distress syndrome

Background:  Airway pressure release ventilation (APRV) is a ventilatory mode, which allows unsupported spontaneous breathing at any phase of the ventilatory cycle. Airway pressure release ventilation as compared with pressure support (PS), another partial ventilatory mode, has been shown to improve gas exchange and cardiac output. We hypothesized whether the use of APRV with maintained unsupported spontaneous breathing as an initial mode of ventilatory support promotes faster recovery from respiratory failure in patients with acute respiratory distress syndrome (ARDS) than PS combined with synchronized intermittent ventilation (SIMV‐group).

Combined effects of prone positioning and airway pressure release ventilation on gas exchange in patients with acute lung injury.

Background: Prone positioning has been shown to improve oxygenation in 60–70% of patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Another way to improve matching of ventilation to perfusion is the use of partial ventilatory support. Preserving spontaneous breathing during mechanical ventilation has been shown to improve oxygenation in comparison with controlled mechanical ventilation. However, no randomized studies are available exploring the effects of preserved spontaneous breathing on gas exchange in combination with prone positioning. Our aim was to determine whether the response of oxygenation to the prone position differs between pressure‐controlled synchronized intermittent mandatory ventilation with pressure support (SIMV‐PC/PS) and airway pressure release ventilation with unsupported spontaneous breathing (APRV).

Arterial Blood Gas Tensions After Resuscitation From Out-of-hospital Cardiac Arrest: Associations With Long-term Neurologic Outcome*

ObjectivesOptimal oxygen and carbon dioxide levels during postcardiac arrest care are currently undefined and observational studies have suggested harm from hyperoxia exposure. We aimed to assess whether mean and time-weighted oxygen and carbon dioxide levels during the first 24 hours of postcardiac arrest care correlate with 12-month neurologic outcome. DesignProspective observational cohort study. SettingTwenty-one ICUs in Finland. PatientsOut-of-hospital cardiac arrest patients treated in ICUs in Finland between March 2010 and February 2011. InterventionsNone. Measurements and Main Results:Arterial blood PaO2 and PaCO2 during the first 24 hours from admission were divided into predefined categories from the lowest to the highest. Proportions of time spent in different categories and the mean PaO2 and PaCO2 values during the first 24 hours were included in separate multivariable regression models along with resuscitation factors. The cerebral performance category at 12 months was used as primary endpoint. A total of 409 patients with arterial blood gases analyzed at least once and with a complete set of resuscitation data were included. The average amount of PaO2 and PaCO2 measurements was eight per patient. The mean 24 hours PaCO2 level was an independent predictor of good outcome (odds ratio, 1.054; 95% CI, 1.006–1.104; p = 0.027) but the mean PaO2 value was not (odds ratio, 1.006; 95% CI, 0.998–1.014; p = 0.149). With multivariate regression analysis, time spent in the PaCO2 band higher than 45 mm Hg was associated with good outcome (odds ratio, 1.015; 95% CI, 1.002–1.029; p = 0.024, for each percentage point increase in time) but time spent in different oxygen categories were not. Conclusions:In this multicenter study, hypercapnia was associated with good 12-month outcome in patients resuscitated from out-of-hospital cardiac arrest. We were unable to verify any harm from hyperoxia exposure. Further trials should focus on whether moderate hypercapnia during postcardiac arrest care improves outcome.

Serum MMP-8, -9 and TIMP-1 in sepsis: high serum levels of MMP-8 and TIMP-1 are associated with fatal outcome in a multicentre, prospective cohort study. Hypothetical impact of tetracyclines.

Recent evidence suggests that matrix metalloproteinases (MMPs) and their endogenous inhibitors are involved in the pathogenesis of sepsis. We studied serum levels of MMP-8, MMP-9 and TIMP-1 (tissue inhibitor of matrix metalloproteinase-1) in a multicentre, prospective cohort study of patients with sepsis treated in Intensive Care Units (ICUs). We analyzed serum samples taken on ICU admission from 248 critically ill sepsis patients. MMP-8, -9 and TIMP-1 serum levels were analyzed by enzyme-linked immunosorbent assays. Serum MMP-8, MMP-9 and TIMP-1 levels were significantly higher in patients with severe sepsis than in healthy controls. Serum MMP-8 levels among non-survivors (n=33) were significantly (p=0.006) higher than among survivors (n=215). Serum TIMP-1 but not MMP-9 levels were significantly higher among non-survivors than survivors (p<0.0001, p=0.079, respectively). Systemic MMP-8 is upregulated in sepsis suggesting that MMP-8 may contribute to the host response during sepsis. High serum MMP-8 and TIMP-1 levels at ICU admission were seen among patients with fatal outcome. With this background, clinical studies examining the ability of MMP-inhibitors (such as the non-antimicrobial properties of tetracyclines) to diminish the MMP-mediated inflammatory response are needed to develop novel therapies in order to improve the outcome of sepsis.

Therapeutic hypothermia after cardiac arrest: implementation and outcome in Finnish intensive care units.

Background:  Therapeutic hypothermia (TH) has been shown to increase survival after out‐of‐hospital resuscitation. The aim of our study was to find out nationwide implementation and the actual utilization of TH after cardiac arrest in Finnish intensive care units (ICUs). We also determined the outcomes and describe demographic variables of the patients treated with TH.

Incidence of iatrogenic dyscarbia during mild therapeutic hypothermia after successful resuscitation from out-of-hospital cardiac arrest.

To investigate the incidence of iatrogenic dyscarbia in survivors of out-of-hospital cardiac arrest treated with induced mild hypothermia.We performed a retrospective cohort study of the ventilatory management based on blood gas analyses of patients resuscitated from prehospital cardiac arrest. In the pilot phase, we assessed the ventilatory management in the patients treated in one university hospital during a 4-year study period. Subsequently, a more recent (1-year) retrospective cohort of resuscitated patients from all five Finnish university hospitals concerning the first 48h after hospital admission was analyzed. Core temperatures and temperature corrected (or non-corrected) blood gas analysis results with focus on carbon dioxide tension were analyzed. In addition, a survey was performed to investigate the ventilatory strategies in all Finnish hospitals providing mild hypothermia for cardiac arrest victims.The pilot cohort suggested a high incidence of hypo- or hyper-carbia during hypothermia treatment. In the multicenter patient population of 122 patients contributing a total of 1627 measurements, the PaCO(2) distribution was as follows: less than 4 kPa in 148 samples out of 1627 (9%), 4-4.6 kPa in 404 (25%), 4.7-6 kPa in 887 (55%) and more than 6 kPa in 188 samples (12%). There was a significant difference in the incidence of hypercarbia between the hospitals (p<0.05).We conclude that normocarbia was achieved/maintained only in approximately 55% of the samples. The incidence of hypo- or hyper-carbia (dyscarbia) was high (45%). This may predispose for serious derangements in the cerebral perfusion of the resuscitated patient. These results call for vigilance in adjustment of the ventilatory management to meet the needs of the patients treated with mild hypothermia.

Late steroid therapy in primary acute lung injury

Objective: To investigate the effect of steroid treatment in the late phase of primary acute lung injury (ALI) with special emphasis on pneumococcal pneumonia. Design: Retrospective study. Setting: Multidisciplinary intensive care unit (ICU) in a university hospital. Patients: Of 31 patients with primary ALI requiring mechanical ventilation for more than 10 days, 16 were treated with methylprednisolone and 15 served as controls. Measurements and results: Steroid and control groups were comparable regarding demographic data, APACHE II score, Multiple Organ Dysfunction Score (MODS), and PaO2/FiO2-ratio on admission to ICU. The mean start of steroid therapy was 9.7 days after establishment of respiratory failure, and values for control patients were registered on day 10. The PaO2/FiO2 ratio improved significantly within 3 days after the start of steroid therapy, and MODS and C-reactive protein decreased concurrently. No differences in mortality, in length of ICU stay, or in length of mechanical ventilation were detectable. In a subgroup analysis, for patients with Streptococcus pneumoniae pneumonia, beneficial change in physiological variables was evident. Conclusions: In patients with primary ALI, steroid therapy, started 10 days after the start of mechanical ventilation, improves gas exchange and is associated with a decrease in multiorgan dysfunction.