Statin therapy in critical illness : an international survey of intensive care physicians' opinions, attitudes and practice

Background Pleotropic effects of statins on inflammation are hypothesised to attenuate the severity of and possibly prevent the occurrence of the host inflammatory response to pathogen and infection-related acute organ failure. We conducted an international survey of intensive care physicians in Australia, New Zealand (ANZ) and United Kingdom (UK). The aims of the survey were to assess the current prescribing practice patterns, attitudes towards prescribing statin therapy in critically ill patients and opinions on the need for an interventional trial of statin therapy in critically ill patients. Methods Survey questions were developed through an iterative process. An expert group reviewed the resulting 26 items for face and content validity and clarity. The questions were further refined following pilot testing by ICU physicians from Australia, Canada and the UK. We used the online Smart SurveyTM software to administer the survey. Results Of 239 respondents (62 from ANZ and 177 from UK) 58% worked in teaching hospitals; most (78.2%) practised in ‘closed’ units with a mixed medical and surgical case mix (71.0%). The most frequently prescribed statins were simvastatin (77.6%) in the UK and atorvastatin (66.1%) in ANZ. The main reasons cited to explain the choice of statin were preadmission prescription and pharmacy availability. Most respondents reported never starting statins to prevent (65.3%) or treat (89.1%) organ dysfunction. Only a minority (10%) disagreed with a statement that the risks of major side effects of statins when prescribed in critically ill patients were low. The majority (84.5%) of respondents strongly agreed that a clinical trial of statins for prevention is needed. More than half (56.5%) favoured rates of organ failure as the primary outcome for such a trial, while a minority (40.6%) favoured mortality. Conclusions Despite differences in type of statins prescribed, critical care physicians in the UK and ANZ reported similar prescription practices. Respondents from both communities agreed that a trial is needed to test whether statins can prevent the onset of new organ failure in patients with sepsis

The diagnostic and prognostic significance of monitoring blood levels of immature neutrophils in patients with systemic inflammation

Introduction: In this cohort study, we investigated whether monitoring blood levels of immature neutrophils (myelocytes, metamyelocytes and band cells) differentiated patients with sepsis from those with the non-infectious (N-I) systemic inflammatory response syndrome (SIRS). We also ascertained if the appearance of circulating immature neutrophils was related to adverse outcome.Methods: Blood samples were routinely taken from 136 critically ill patients within 48 hours of ICU entry and from 20 healthy control subjects. Clinical and laboratory staff were blinded to each other's results, and patients were retrospectively characterised into those with SIRS (n = 122) and those without SIRS (n = 14). The patients with SIRS were further subdivided into categories of definite sepsis (n = 51), possible sepsis (n = 32) and N-I SIRS (n = 39). Two established criteria were used for monitoring immature white blood cells (WBCs): one where band cells &gt;10% WBCs and the other where &gt;10% of all forms of immature neutrophils were included but with a normal WBC count. Immature neutrophils in blood smears were identified according to nuclear morphology and cytoplasmic staining.Results: With the first criterion, band cells were present in most patients with SIRS (mean = 66%) when compared with no SIRS (mean = 29%; P &lt;0.01) and with healthy subjects (0%). The prevalence of band cells was higher in definite sepsis (mean = 82%) than in patients with possible sepsis (mean = 63%; P &lt;0.05) or with N-I SIRS (mean = 39%; P &lt;0.001), and they had a sensitivity of 84% and a specificity of 71% for the detection of definite sepsis. With the second criterion (that is, patients with normal WBC counts), we noted that immature neutrophils did not differentiate any of the patient groups from one another. Patients who died within 1 week of blood sample provision had higher levels of myelocytes and metamyelocytes (median = 9%; P &lt;0.05) than patients who died at 2 to 4 weeks (median = 0.5%).Conclusions: Raised blood levels of band cells have diagnostic significance for sepsis, provided that measurements are not confined to patients with normal WBC counts, whereas an increased prevalence of myelocytes and metamyelocytes may have prognostic application.</p

Long-term ill health in sepsis survivors: An ignored healthcare challenge?

Initiated by the Global Sepsis Alliance in 2012, September 13th every year is denoted as World Sepsis Day. Sepsis remains a global healthcare problem, affecting all age groups. The extrapolated annual incidence of ~49 million cases (with ~20 million cases in children under 5-years of age) and 11 million deaths, generates ~38 million sepsis survivors per year1. There is tacit acknowledgement that sepsis survivorship is a major cause of health loss globally. However, currently, no healthcare system globally (including the United Kingdom National Health Service (NHS)), can claim to have a structured approach to improving sepsis survivorship to all those who recover from an index sepsis episode. It is in this context that we provide an overview of domains of long-term ill health in sepsis survivors, highlight illustrative knowledge gaps and the need for a structured approach to improve sepsis survivorship

Can concurrent abnormalities in free light chains and immunoglobulin concentrations identify a target population for immunoglobulin trials in sepsis?

Objectives: Light chains κ and λ are immunoglobulin constituents but also circulate independently in blood as free light chains. We investigated whether a concomitant abnormality in free light chain and immunoglobulin levels could identify a high risk of death sepsis subpopulation to inform future IV immunoglobulin trials. We tested whether light chain allelic inclusion occurs in circulating B cells.Design: Prospective cohort study.Setting: Adult general ICUs.Patients: Adult sepsis patients without any documented immune comorbidity.Interventions: None.Measurements and Main Results: Serum total free light chain, immunoglobulin G, immunoglobulin A, and immunoglobulin M were measured on ICU days 1, 3, and 7. Population normal ranges defined normal and abnormal categories. Logistic regression models tested any independent relationship between high free light chain, immunoglobulins and hospital mortality. CD19 B-cell subsets expressing cell surface κ and λ were quantified by flow cytometry; their frequencies were compared against healthy subjects and correlation assessed against free light chain concentrations. On ICU day 1, high free light chain λ and high free light chain κ were seen in 46.5% and 75.3% of the study cohort (n = 101). Low immunoglobulin levels were commonplace (45.5%) at ICU admission. ICU admission day free light chain and immunoglobulin concentrations were significantly correlated. Septic patients had significantly more CD19 B cells expressing both κ and λ compared with healthy controls (median [interquartile range] 4.1% [2.4–11.0] vs 1.3% [1.2–2.9], respectively; p = 0.0001); these correlated with free light chain concentrations.Conclusions: To our knowledge, abnormalities and associations of free light chain in critically ill adults with sepsis have not been previously reported. The additional prognostic value of free light chain λ and the significance of allelic inclusion in B cells in sepsis require further investigation

Septic shock resuscitation in the first hour

PURPOSE OF REVIEW: We reviewed the recent advances in the initial approach to resuscitation of sepsis and septic shock patients.RECENT FINDINGS: Sepsis and septic shock are life-threatening emergencies. Two key interventions in the first hour include timely antibiotic therapy and resuscitation. Before any laboratory results, the need for resuscitation is considered if a patient with suspected infection has low blood pressure (BP) or impaired peripheral circulation found at clinical examination. Until now, this early resuscitation in sepsis and septic shock was supported by improvements in outcome seen with goal-directed therapy. However, three recent, goal-directed therapy trials failed to replicate the originally reported mortality reductions, prompting a debate on how this early resuscitation should be performed. As resuscitation is often focussed on macrociculatory goals such as optimizing central venous pressure, the discordance between microcirculatory and macrocirculatory optimization during resuscitation is a potential argument for the lack of outcome benefit in the newer trials. Vasoactive drug dose and large volume resuscitation-associated-positive fluid balance, are independently associated with worse clinical outcomes in critically ill sepsis and septic shock patients. As lower BP targets and restricted volume resuscitation are feasible and well tolerated, should we consider a lower BP target to reduce the adverse effects of catecholamine' and excess resuscitation fluids. Evidence guiding fluids, vasopressor, and inotrope selection remains limited.SUMMARY: Though the early resuscitation of sepsis and septic shock is key to improving outcomes, ideal resuscitation targets are elusive. Distinction should be drawn between microcirculatory and macrocirculatory changes, and corresponding targets. Common components of resuscitation bundles such as large volume resuscitation and high-dose vasopressors may not be universally beneficial. Microcirculatory targets, individualized resuscitation goals, and reassessment of completed trials using the updated septic shock criteria should be focus areas for future research.</p

Activated protein C in severe acute pancreatitis without sepsis? Not just yet ...

Severe acute pancreatitis (SAP) is characterized by an unregulated systemic proinflammatory response secondary to activation of trypsin within the pancreatic tissue, resulting in multiple organ failure. This dysregulated inflammation leading to organ dysfunction also characterizes severe sepsis. Activated protein C (APC) has pleotropic effects on the immune, coagulation, inflammatory and apoptotic pathways, and has been postulated to benefit acute pancreatitis - although concerns of possible retroperitoneal bleeding remain. Currently, experimental studies and subgroup data on patients with pancreatitis from a randomized controlled trial of APC in severe sepsis form the literature on the possible role of APC in SAP. We review the first randomized controlled trial of APC in acute pancreatitis published in the present issue of Critical Care