Unsatisfactory Short-Term Neurodevelopmental Outcomes of Preterm Infants Who Received Polymyxin B-Immobilized Fiber Column-Direct Hemoperfusion for Septic Shock.

Sepsis and septic shock are associated with high mortality and neurodevelopmental impairment in preterm infants. Recently, endotoxin and mediator removal using a polymyxin B-immobilized fiber column for direct hemoperfusion (PMX-DHP) has been used for the management of septic shock even in neonates. Although early withdrawal from shock with PMX-DHP contributes to survival, its effect on neurodevelopment after discharge is unclear. This study aimed to examine short-term neurodevelopmental impairment in preterm infants with septic shock who were treated with PMX-DHP. We retrospectively assessed five infants who received treatment with PMX-DHP (median 25.5 [interquartile range: 24.8-28.3] weeks and 817 [interquartile range: 667-954] g). Neurodevelopmental outcomes were assessed with the Kyoto Scale of Psychological Development 2001 at a median 34.5 (interquartile range: 29.5-44.5) months of corrected age after discharge. The short-term neurodevelopmental prognosis of preterm infants treated with PMX-DHP for septic shock was delayed (overall developmental quotient < 70) with an average quotient of 57.3. Furthermore, four (80%) of five patients presented with intraventricular hemorrhage and another four (80%) with periventricular leukomalacia. In conclusion, preterm infants with septic shock treated with PMX-DHP had unsatisfactory short-term neurodevelopmental outcomes. Hence, the effect of PMX-DHP in improving neurodevelopmental prognosis even in preterm infants with septic shock should be further evaluated.

A Multicenter Survey of House Staff Knowledge About Sepsis and the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock".

BACKGROUND: We aimed to assess the knowledge, attitudes, and perceptions of resident physicians regarding sepsis in general and the Surviving Sepsis Campaign Guidelines in particular. METHODS: After institutional review board approval, we surveyed internal medicine (IM) and emergency medicine (EM) house staff from 3 separate institutions. House staff were notified of the survey via e-mail from their residency director or chief resident. The survey was Internet-based (using http://www.surveymonkey.com ), voluntary, and anonymous. The Surviving Sepsis Campaign Guidelines were used to develop the survey. The survey was open between December 2015 and April 2016. No incentives for participation were given. Reminder e-mails were sent approximately every 3 to 4 weeks to all eligible participants. Comparisons of responses were evaluated using the N-1 2-proportion test. RESULTS: A total of 133 responses were received. These included 84 from IM house staff, 27 from EM house staff, and 22 who selected "other." Eighty (101/126) percent reported managing at least 1 patient with sepsis in the preceding 30 days, 85% (97/114) rated their knowledge of the Surviving Sepsis Guidelines as "very familiar" or at least "somewhat familiar," and 84% (91/108) believed their training in the diagnosis and management of sepsis was "excellent" or at least "good." However, 43% (47/108) reported not receiving any feedback on their treatment of patients with sepsis in the last 30 days, while 24% (26/108) received feedback once. Both IM and EM house staff received comparable rates of feedback (62% vs 48%, respectively; P = .21). For the 3 questions that directly tested knowledge of the guidelines, the scores of the IM and EM house staff were similar. Notably, <20% of both groups correctly identified diagnostic criteria for sepsis. CONCLUSION: Additional education of IM and EM house staff on the Surviving Sepsis Campaign Guidelines is warranted, along with more consistent feedback regarding their diagnosis and management of sepsis.

Gender differences in mortality and quality of life after septic shock: A post-hoc analysis of the ARISE study.

PURPOSE: To assess the impact of gender and pre-menopausal state on short- and long-term outcomes in patients with septic shock. MATERIAL AND METHODS: Cohort study of the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial, an international randomized controlled trial comparing early goal-directed therapy (EGDT) to usual care in patients with early septic shock, conducted between October 2008 and April 2014. The primary exposure in this analysis was legal gender and the secondary exposure was pre-menopausal state defined by chronological age (≤ 50 years). RESULTS: 641 (40.3%) of all 1591 ARISE trial participants in the intention-to-treat population were females and overall, 337 (21.2%) (146 females) patients were 50  years of age or younger. After risk-adjustment, we could not identify any survival benefit for female patients at day 90 in the younger (≤50 years) (adjusted Odds Ratio (aOR): 0.91 (0.46-1.89), p = .85) nor in the older (>50 years) age-group (aOR: 1.10 (0.81-1.49), p = .56). Similarly, there was no gender-difference in ICU, hospital, 1-year mortality nor quality of life measures. CONCLUSIONS: This post-hoc analysis of a large multi-center trial in early septic shock has shown no short- or long-term survival effect for women overall as well as in the pre-menopausal age-group.

Conservative vs liberal fluid therapy in septic shock (CLASSIC) trial-Protocol and statistical analysis plan.

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 thus 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 Intensive Care (CLASSIC) trial. The aim of the CLASSIC trial is to assess benefits and harms of IV fluid restriction versus standard care in adult intensive care unit (ICU) patients with septic shock. METHODS: CLASSIC trial is an investigator-initiated, international, randomised, stratified, and analyst-blinded trial. We will allocate 1554 adult patients with septic shock, who are planned to be or are admitted to an ICU, to IV fluid restriction versus standard care. The primary outcome is mortality at day 90. Secondary outcomes are serious adverse events (SAEs), serious adverse reactions (SARs), days alive at day 90 without life support, days alive and out of the hospital at day 90 and mortality, health-related quality of life (HRQoL), and cognitive function at 1 year. We will conduct the statistical analyses according to a pre-defined statistical analysis plan, including three interim analyses. For the primary analysis, we will use logistic regression adjusted for the stratification variables comparing the two interventions in the intention-to-treat (ITT) population. DISCUSSION: The CLASSIC trial results will provide important evidence to guide clinicians' choice regarding the IV fluid therapy in adults with septic shock.

Quality of life assessment following amputation for septic shock: a long-term descriptive survey after symmetric peripheral gangrene.

PURPOSE: To assess health-related quality of life (HRQOL) following rehabilitation of amputees suffering symmetric peripheral gangrene (SPG) after septic shock. MATERIAL AND METHODS: A retrospective cohort study was conducted in nine French specialized rehabilitation centers. Thirty-two ICU adult patients hospitalized between 2005 and 2015 for septic shock who additionally presented with SPG resulting in at least two major amputations were enrolled. HRQOL was assessed by EQ-5D-3 L questionnaire. RESULTS: All patients (mean ICU length of stay 39 ±â€¯22d, SAPS II 58 ±â€¯18) had both lower limbs amputated and 84% were quadruple amputees. HRQOL, assessed 4.8 ±â€¯2.8 years after amputation, was inferior to the French reference. However, patients' self-rated health status was similar to the reference at the time of HRQOL assessment. The main factor of impaired HRQOL was intense phantom pain, not the mobility or self-care dimensions of EQ-5D. All patients except one preferred to be treated again for SPG despite disability. CONCLUSION: ICU survivors referred to rehabilitation centers after SPG-related amputations had impaired HRQOL. At the time of HRQOL assessment, they considered themselves in good health and preferred to be treated again despite disability. Appraisal of long-term functional outcome should not be used to guide end-of-life decision-making in this situation.

Factors Associated With Short and Long Term Cognitive Changes in Patients With Sepsis.

This study aimed to assess cognition in patients with severe sepsis or septic shock and whether cognitive impairment was associated with clinical and laboratory parameters. We conducted a cohort study of patients with severe sepsis and septic shock evaluated within 24 h and one year after ICU discharge. Demographic, clinical and laboratory data were analyzed, and the following neuropsychological tests were applied: Consortium to Establish Registry for Alzheimer's Disease, Mini-Mental State Examination, and Trail Making Test forms A and B. We included 33 patients, mean age of 49, 19% were female. Patients underperformed on most measures 24 h after ICU discharge, with improvement on follow-up. IQCODE, APACHE II scores, NSE and IFN-γ levels at ICU discharge were associated with poor cognitive performance, while higher educational level was associated with good cognitive performance. The time to first antibiotic dose, accumulated dose of haloperidol during UCI stay and mean glycemia were also associated with poor cognitive outcome. In general, patients with severe sepsis or septic shock have cognitive impairment that can improve over time. This improvement was associated with factors identified during their ICU stay, such as cognitive reserve, educational level, mean glycemia during ICU stay and NSE level.

Factors associated with non-response at health-related quality of life follow-up in a septic shock trial.

BACKGROUND: Follow-up of intensive care unit (ICU) patients often includes health-related quality of life (HRQoL) surveying, but non-responders hamper the interpretation. Our aim was to assess factors for non-response to HRQoL survey in ICU patients with septic shock at follow-up in a clinical trial. METHODS: In a post hoc follow-up registry study, we assessed all the Danish survivors in the Transfusion-Requirements in Septic Shock trial patients, who were mailed the Short Form 36-item Survey (SF-36) 1-year after randomization. We used covariates from the trial database merged with covariates from nation-wide registries using the unique national identification number to explore possible factors for not responding. Five covariates were pre-specified to be included in the primary multivariate analysis: age, number of days in hospital from randomization to follow-up, level of education, cohabitation and employment status at follow-up. We compared the mortality from 1-year survival (2012-2014) till end of final follow-up (January 2016) between non-responders and responders. RESULTS: We assessed 308 survivors of whom 108 (35%) were non-responders. In the primary analysis lower age (odds ratio 1.03, 95% CI [1.01-1.05]), more admission days in hospital (1.006 [1.001-1.011]) and living alone (4.33 [2.46-7.63]) were associated with non-responding, whereas the level of education and employment status were not. Non-responders had a hazard ratio of 1.63 [0.97-2.72] for mortality from 1-year follow-up to final follow-up as compared to the responders. CONCLUSION: Being younger, spending more days in hospital and living alone were all associated with non-response at 1-year HRQoL follow-up among ICU patients with septic shock.

Low quality of dying and death in patients with septic shock as perceived by nurses and resident physicians.

Septic shock is a disease with both high prevalence and mortality. Few studies have evaluated the quality of dying and death (QODD) in patients with septic shock. The authors compared the QODD of patients who died of septic shock versus other causes. They prospectively collected QODD surveys from nurses and residents caring for 196 patients who died in the medical intensive care unit (ICU) at an urban, university hospital. Patients were included in the analysis if either a nurse or resident returned a survey. Chart review established cause of death. The authors compared total QODD scores (on a scale of 0-100) and a single-item score (QODD-1; on a scale of 0-10) of patients who died of septic shock versus other causes. Survey response rates were 59% (n = 155) for residents and 49% (n = 129) for nurses. Nurses rated patients as having lower total QODD and QODD-1 scores for septic (Δ 7.5 points, p = 0.03, and 0.9 points, p = 0.05, respectively). Residents rated septic patients with lower QODD-1 scores than nonseptic patients (Δ 0.8 points, p = 0.03). This study shows that nurses rate patients with septic shock as having lower QODD than patients dying of other causes. These findings are important for clinicians who counsel families of patients dying of septic shock.

Endogenous interleukin 18 regulates testicular germ cell apoptosis during endotoxemia.

Orchitis (testicular swelling) often occurs during systemic inflammatory conditions, such as sepsis. Interleukin 18 (IL18) is a proinflammatory cytokine and is an apoptotic mediator during endotoxemia, but the role of IL18 in response to inflammation in the testes was unclear. WT and IL18 knockout (KO) mice were injected lipopolysaccharide (LPS) to induce endotoxemia and examined 12 and 48  h after LPS administration to model the acute and recovery phases of endotoxemia. Caspase activation was assessed using immunohistochemistry. Protein and mRNA expression were examined by western blot and quantitative real-time RT-PCR respectively. During the acute phase of endotoxemia, apoptosis (as indicated by caspase-3 cleavage) was increased in WT mice but not in IL18 KO mice. The death receptor-mediated and mitochondrial-mediated apoptotic pathways were both activated in the WT mice but not in the KO mice. During the recovery phase of endotoxemia, apoptosis was observed in the IL18 KO mice but not in the WT mice. Activation of the death-receptor mediated apoptotic pathway could be seen in the IL18 KO mice but not the WT mice. These results suggested that endogenous IL18 induces germ cell apoptosis via death receptor mediated- and mitochondrial-mediated pathways during the acute phase of endotoxemia and suppresses germ cell apoptosis via death-receptor mediated pathways during recovery from endotoxemia. Taken together, IL18 could be a new therapeutic target to prevent orchitis during endotoxemia.

[Neurological and psychological long-term effects of sepsis]. / Neurologische und psychische Langzeitfolgen der Sepsis.

BACKGROUND: In addition to the limitations to the health-related quality of life that have been compiled with validated test instruments, a number of former sepsis patients suffer from functional impairments, which are categorized under the terms critical illness polyneuropathy (CIP) or critical illness myopathy (CIM), which have been in existence for over 20 years now. CURRENT FOCUS: The issues of delirium during intensive therapy and persistent residual neurocognitive impairments, posttraumatic stress disorder (PTSD) and states of depression related to perihospital functional development have increasingly attracted notice. FUTURE: The degree of functional deficits resulting from sepsis and the actual quality of life of those affected may, however, be influenced by taking appropriate rehabilitation measures. However, neither therapeutic rehabilitation standards nor any rehabilitation facilities tailored to the needs of these patients currently exist.

Survivors of septic shock caused by Neisseria meningitidis in childhood: psychosocial outcomes in young adulthood.

OBJECTIVE: To investigate long-term psychosocial outcomes in young adults who survived septic shock caused by Neisseria meningitidis (meningococcal septic shock) during childhood. DESIGN: A cross-sectional study. SETTING: The psychological investigation took place in the department of Child and Adolescent Psychiatry of the Erasmus MC-Sophia Children's Hospital. PATIENTS: All consecutive surviving patients with meningococcal septic shock requiring intensive care treatment at the pediatric intensive care unit between 1988 and 2001. INTERVENTION: To explore biographical characteristics (such as living conditions, educational, occupational, and marital status) and illness-related physical or social consequences a structured interview was used. To assess intellectual functioning the Groninger Intelligence Test 2 was used and to assess behavioral/emotional problems, the Adult Self-Report was used. MEASUREMENTS AND MAIN RESULTS: Fifty-eight of 83 eligible septic shock survivors were evaluated (response rate: 70%). The patients were 16-31 yrs old at time of follow-up (median age: 21 yrs old). These patients had had meningococcal septic shock before 18 yrs of age. Median follow-up interval was 13 yrs, with a range of 4 to 16 yrs. For the vast majority of meningococcal septic shock patients, outcomes on biographical characteristics, intellectual functioning, and levels of behavioral/emotional problems were comparable to those of reference groups. A minority (5% to 20%) still report illness-related physical or social consequences, behavioral and emotional problems, and lower intellectual functioning. CONCLUSIONS: Despite favorable outcomes for the majority of meningococcal septic shock patients in the long term, an important minority (5% to 20%) still struggles with ongoing problems as to behavioral/emotional problems, intellectual functioning, biographical characteristics, and illness-related physical or social consequences.

A reflection from the other side of the bed--an account of what it is like to be a patient and a relative in an intensive care unit.

Following a two-day history of pyrexia, stomach pain, diarrhoea and an emergency laparotomy my wife was admitted to an intensive care unit (ICU) with septic shock. Lucy was artificially ventilated for seven days, and was treated with fluids, vasopressors and antibiotics. Her condition continued to deteriorate and on about the third day she looked as though she might die. However over the next few days Lucy began to recover and she was eventually transferred to a ward and came home three weeks after admission to hospital. During her stay in the intensive care unit, Lucy developed pneumonia, bilateral pleural effusions, acute renal failure and a pericardial effusion. Over the weeks and months that followed, Lucy began to describe her experiences and the impact that these have had on her. She described what it felt like to be a patient in the ICU and the challenges that she faced during her recovery. I am a Registered Nurse and at the time my wife was admitted to the ICU I had spent twenty years working within the field of intensive care. Until my wife had been admitted to ICU, I thought that I had a good appreciation of what it was like to be a patient or a relative in an intensive care unit. Having experienced critical care at first hand and having had an opportunity to reflect on what happened I now realise what little insight I had. I have now come to realise that as nurses in intensive care there is much we can do to alleviate the suffering and discomfort experienced by some of our patients and relatives. Perhaps by describing what happened, I will enable the reader to understand more clearly and to reflect on those factors which have a deep and lasting impact on patients and their relatives and which can be influenced by nurses at the bedside. For the purpose of this account, I have chosen to call my wife, Lucy.

Sacroiliitis infected with group A streptococcus in a child presenting with confusion and combativeness.

Group A streptococcus-associated severe invasive infection (streptococcal toxic shock syndrome) has been described. Streptococcal toxic shock syndrome occurs when the infecting strain of group A streptococcus produces superantigens. Confusion and combativeness are well known as the common symptoms of streptococcal toxic shock syndrome. We encountered a child who suffered from pyogenic sacroiliitis, with confusion and combativeness. Group A streptococcus was isolated from the patient's blood culture. However, his disease did not fulfill the criteria of streptococcal toxic shock syndrome. Pyogenic sacroiliitis in children is rare, but patients with pyogenic sacroiliitis due to group A streptococcus infection could show confusion and combativeness as clinical signs, similar to the signs in streptococcal toxic shock syndrome.

An explorative study on quality of life and psychological and cognitive function in pediatric survivors of septic shock.

OBJECTIVE: To evaluate self-reported health-related quality of life, anxiety, depression, and cognitive function in pediatric septic shock survivors. DESIGN: A retrospective cohort study. SETTING: A 14-bed tertiary pediatric intensive care unit. PATIENTS: Children aged >or=8 yrs at the time of the follow-up who were admitted between 1995 and 2004 for septic shock. Inotropic and or vasoconstrictive agents were administered to these patients for >or=24 hrs. INTERVENTION: Health-related quality of life was assessed with the KIDSCREEN-52, anxiety with the State Trait Anxiety Inventory for Children, depression with the Children's Depression Inventory, and cognitive function with the cognitive scale of the TNO-AZL Children's Quality of Life Questionnaire Child Form. MEASUREMENTS AND MAIN RESULTS: Fifty of 82 eligible pediatric septic shock survivors were evaluated. The median age of the children at pediatric intensive care unit admission was 4.2 yrs (range, 0.0-17.0 yrs); the median age at follow-up was 10.7 yrs (range, 8.0-20.4 yrs). Health-related quality of life and anxiety scores were comparable to the age-related Dutch norm population. Depression scores were significantly better than the norm population, whereas cognitive function was significantly lower than the norm population. We found that 44% of the children had cognitive scores <25% of the norm population. Young age at the time of pediatric intensive care unit admission was predictive of cognitive problems, and cognitive problems were associated with lower emotional function. CONCLUSIONS: In this group of septic shock survivors, health-related quality of life, anxiety, and depression are equal to or slightly better than the age-related Dutch norm population. Cognitive function is decreased, especially in children admitted at younger ages. Follow-up studies with adequate neuropsychological testing are warranted to evaluate the association between septic shock, cognitive function, and risk factors for cognitive problems.

Long-term cognitive functioning in children and adolescents who survived septic shock caused by Neisseria meningitidis.

AIMS: To assess long-term cognitive functioning and its predictors, in children and adolescents who survived meningococcal septic shock (MSS) 4 to 16 years ago. METHODS: The Wechsler Intelligence Scale for Children-third edition was used to measure intellectual functioning and neuropsychological tests were used to measure attention, verbal memory, visual-motor integration, and executive skills. RESULTS: Overall, results of the total MSS sample (N=77) as to neuropsychological functioning were similar to those of normative reference groups. On social and practical reasoning and visual-motor integration, however, MSS children obtained poorer outcomes compared to normative data. Two children had mental retardation (estimated IQ<70) due to the MSS. The percentage of children with mental retardation or borderline intellectual functioning (15%) was similar to that in the general population (16%). Eighteen children (23%) had a z score<-2, indicating unusual poor functioning, on one or more domains of neuropsychological functioning (selective attention, sustained attention, and executive functioning). Compared to normative data, significantly more children had received special education services in the past. Older age at time of follow-up was the most important significant predictor of poorer long-term cognitive functioning. CONCLUSION: Overall, long-term outcomes as to cognitive functioning of the total MSS sample were similar to those of normative reference groups, but MSS children showed long-term impairments on social and practical reasoning, visual-motor integration, attention, and executive functioning. Older age at time of follow-up was a significant predictor.

Self-esteem in children and adolescents after septic shock caused by Neisseria meningitidis: scars do matter.

PURPOSE: To investigate self-esteem and its relation to scars, amputations, and orthopedic sequelae in children and adolescents long term after meningococcal septic shock (MSS) caused by Neisseria meningitidis. METHODS: The Dutch versions of the Self-Perception Profile for Children (SPP-C; 8-11 years) and the Self-Perception Profile for Adolescents (SPP-A; 12-17 years) were used to assess self-esteem. The Patient and Scar Assessment Scale (PSAS) was used to evaluate scar severity. RESULTS: MSS boys aged 8-11 years achieved higher, more favorable scores on self-esteem, whereas same-aged MSS girls reported comparable levels of self-esteem compared with the respectively same-aged reference boys and girls. MSS boys and girls aged 12-17 years obtained unfavorable scores on self-esteem compared with respectively same-aged reference boys and girls. Overall gender did not have an effect on self-esteem. Severity of illness, age at time of illness, and age at time of follow-up were not significant predictors of self-esteem. MSS adolescents with scars reported lower global self-worth than MSS adolescents without scars. The worse MSS children evaluated their scars, the worse their outcomes on social acceptance. The worse MSS adolescents evaluated their scars, the worse their outcomes on close friendship, but the better their outcomes on social acceptance and behavioral conduct. CONCLUSION: In this cross-sectional study, favorable outcomes for self-esteem were found in MSS children, whereas MSS adolescents reported lower self-esteem compared with reference adolescents. Adolescents with scars reported lower global self-worth than MSS adolescents without scars.

Surviving meningococcal septic shock: health consequences and quality of life in children and their parents up to 2 years after pediatric intensive care unit discharge.

OBJECTIVE: To assess health consequences and health-related quality of life (HR-QoL) in children with meningococcal septic shock up to 2 yrs after discharge from the pediatric intensive care unit and to assess their parents. To determine major predictors of that outcome. PATIENTS AND METHODS: A prospective cohort study. Follow-up of all consecutive children with septic shock and purpura requiring intensive care treatment between 2001 and 2005, and their parents. HR-QoL was assessed with the Child Health Questionnaire (children) and Medical Outcomes Study 36-item Short-Form Health Survey (parents). RESULTS: Of 53 eligible families, 47 participated (28 boys/19 girls; median age at the time of pediatric intensive care unit admission, 3.7 yrs; median Pediatric Risk of Mortality score, 21). A total of 26 children (55%) had scars as a result of skin necrosis; two (4%) had amputation of a digit or digits. In 21 children (45%), chronic complaints were reported. Children with and without chronic complaints did not differ significantly with regard to severity of illness and age at the time of pediatric intensive care unit admission. Significantly lower scores were found on HR-QoL scales concerning mainly physical functioning and health perception in comparison with normative data. There was a significant negative association between severity of illness and the HR-QoL scale concerning physical functioning. Children with chronic complaints had significantly lower scores on the HR-QoL scale concerning pain. Eight of 47 mothers (17%) at the time of the study had anxiety or depression requiring professional help. Mothers with and without these problems differed significantly with regard to age of their child at the time of pediatric intensive care unit admission. Parents showed significantly higher scores on HR-QoL scales concerning physical functioning and bodily pain in comparison with normative data. There was a significantly negative association between the presence of emotional problems and HR-QoL scores in mothers. CONCLUSIONS: Up to 2 yrs after discharge from the pediatric intensive care unit, there is still a considerable effect on health and HR-QoL in children, especially on the physical scales. Severity of illness and chronic complaints negatively affected HR-QoL scales in children. Quite a few mothers suffered from emotional problems.