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Tuesday, 2 April 2019

Focus on ethics and palliative care in the intensive care unit

By: Courtright, K.R., Benoit, D.D. & Curtis, J.R.

Intensive Care Med (04/2019) First online: 25 March 2019

This focus editorial highlights papers on prognostic and palliative care strategies for critically ill patients and their families that were published in Intensive Care Medicine (ICM) and other journals in the last 2 years, including five original research papers, one systematic review, one pragmatic review, six “what’s new”, two “understanding the disease”, and one editorial.

A decade of progress in critical care echocardiography: a narrative review

By: Vieillard-Baron, A., Millington, S.J., Sanfillipo, F. et al.

Intensive Care Med (04/2019). P1-19 – first online: 25th March 2019

This narrative review focusing on critical care echocardiography (CCE) has been written by a group of experts in the field, with the aim of outlining the state of the art in CCE in the 10 years after its official recognition and definition.
In the last 10 years, CCE has become an essential branch of critical care ultrasonography and has gained general acceptance. Its use, both as a diagnostic tool and for hemodynamic monitoring, has increased markedly, influencing contemporary cardiorespiratory management. Recent studies suggest that the use of CCE may have a positive impact on outcomes. CCE may be used in critically ill patients in many different clinical situations, both in their early evaluation of in the emergency department and during intensive care unit (ICU) admission and stay. CCE has also proven its utility in perioperative settings, as well as in the management of mechanical circulatory support. CCE may be performed with very simple diagnostic objectives. This application, referred to as basic CCE, does not require a high level of training. Advanced CCE, on the other hand, uses ultrasonography for full evaluation of cardiac function and hemodynamics, and requires extensive training, with formal certification now available. Indeed, recent years have seen the creation of worldwide certification in advanced CCE. While transthoracic CCE remains the most commonly used method, the transesophageal route has gained importance, particularly for intubated and ventilated patients.
CCE is now widely accepted by the critical care community as a valuable tool in the ICU and emergency department, and in perioperative settings.

Continuous Electroencephalography After Moderate to Severe Traumatic Brain Injury

 by Lee, Hyunjo; Mizrahi, Moshe A.; Hartings, Jed A.; Sharma, Sameer; Pahren, Laura; Ngwenya, Laura B.; Moseley, Brian D.; Privitera, Michael; Tortella, Frank C.; Foreman, Brandon  

Objectives: After traumatic brain injury, continuous electroencephalography is widely used to detect electrographic seizures. With the development of standardized continuous electroencephalography terminology, we aimed to describe the prevalence and burden of ictal-interictal patterns, including electrographic seizures after moderate-to-severe traumatic brain injury and to correlate continuous electroencephalography features with functional outcome.
Design: Post hoc analysis of the prospective, randomized controlled phase 2 multicenter INTREPID2566 study (ClinicalTrials.gov: NCT00805818). Continuous electroencephalography was initiated upon admission to the ICU. The primary outcome was the 3-month Glasgow Outcome Scale-Extended. Consensus electroencephalography reviews were performed by raters certified in standardized continuous electroencephalography terminology blinded to clinical data. Rhythmic, periodic, or ictal patterns were referred to as “ictal-interictal continuum”; severe ictal-interictal continuum was defined as greater than or equal to 1.5 Hz lateralized rhythmic delta activity or generalized periodic discharges and any lateralized periodic discharges or electrographic seizures. Setting: Twenty U.S. level I trauma centers.
Patients: Patients with nonpenetrating traumatic brain injury and postresuscitation Glasgow Coma Scale score of 4–12 were included.
Interventions: None.
Measurements and Main Results: Among 152 patients with continuous electroencephalography (age 34 ± 14 yr; 88% male), 22 (14%) had severe ictal-interictal continuum including electrographic seizures in four (2.6%). Severe ictal-interictal continuum burden correlated with initial prognostic scores, including the International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (r = 0.51; p = 0.01) and Injury Severity Score (r = 0.49; p = 0.01), but not with functional outcome. After controlling clinical covariates, unfavorable outcome was independently associated with absence of posterior dominant rhythm (common odds ratio, 3.38; 95% CI, 1.30–9.09), absence of N2 sleep transients (3.69; 1.69–8.20), predominant delta activity (2.82; 1.32–6.10), and discontinuous background (5.33; 2.28–12.96) within the first 72 hours of monitoring.
Conclusions: Severe ictal-interictal continuum patterns, including electrographic seizures, were associated with clinical markers of injury severity but not functional outcome in this prospective cohort of patients with moderate-to-severe traumatic brain injury. Importantly, continuous electroencephalography background features were independently associated with functional outcome and improved the area under the curve of existing, validated predictive models.

Evolution and Impact of Thrombocytopenia in Septic Shock: A Retrospective Cohort Study

 by Menard, Chantalle E.; Kumar, Anand; Houston, Donald S.; Turgeon, Alexis F.; Rimmer, Emily; Houston, Brett L.; Doucette, Steven; Zarychanski, Ryan  

Objectives: To characterize the prevalence, incidence, and temporal evolution of thrombocytopenia (platelets < 100 × 109/L) in septic shock and to investigate the independent association of thrombocytopenia on clinical outcomes.
Design: Retrospective, propensity-matched, cohort study.
Setting: Two academic ICUs in Winnipeg, Canada.
Patients: Nine-hundred eighty adult patients diagnosed with septic shock between 2007 and 2012. Interventions: Propensity-matched cohort analysis and Cox proportional hazard model evaluating thrombocytopenia over time.
Measurements and Main Results: Of 980 adults, 165 patients (16.8%) had thrombocytopenia at ICU admission (prevalent), whereas 271 (27.7%) developed thrombocytopenia during ICU admission (incident). Among patients with incident thrombocytopenia, the median time from ICU admission to thrombocytopenia was 2 days (interquartile range, 1–3 d). Among survivors, the median time from incident thrombocytopenia to platelet recovery was 6 days (interquartile range, 4–8 d). The median time from liberation of vasopressors to recovery of platelets concentration (≥ 100 × 109/L) was 2 days (interquartile range, 0–4 d). In a propensity-matched analysis, thrombocytopenia was associated with increased durations of ICU length of stay (9 vs 6 d; p < 0.01), mechanical ventilation (7 vs 4 d; p < 0.01), and vasopressor use (4 vs 3 d; p < 0.01), as well as increased major bleeding events (41% vs 18%; p < 0.01). In an adjusted Cox proportional hazards model, thrombocytopenia was significantly associated with both increased ICU mortality (hazard ratio, 1.99; 95% CI, 1.51–2.63) and hospital mortality (hazard ratio, 1.93; 95% CI, 1.48–2.51).
Conclusions: Both the prevalence and incidence of thrombocytopenia are high in septic shock. Incident thrombocytopenia occurs early in septic shock, and platelet recovery lags behind clinical recovery. In septic shock, thrombocytopenia is associated with increased length of stay, longer duration of organ support, major bleeding events, and mortality.

Evaluation of Medication Errors at the Transition of Care From an ICU to Non-ICU Location

 by Tully, Andrea P.; Hammond, Drayton A.; Li, Chenghui; Jarrell, Andrew S.; Kruer, Rachel M.

Objectives: To determine the point prevalence of medication errors at the time of transition of care from an ICU to non-ICU location and assess error types and risk factors for medication errors during transition of care. 
Design: This was a multicenter, retrospective, 7-day point prevalence study. 
Setting: Fifty-eight ICUs within 34 institutions in the United States and two in the Netherlands. Patients: Nine-hundred eighty-five patients transferred from an ICU to non-ICU location. Interventions: None. 
Measurements and Main Results: Of 985 patients transferred, 450 (45.7%) had a medication error occur during transition of care. Among patients with a medication error, an average of 1.88 errors per patient (SD, 1.30; range, 1–9) occurred. The most common types of errors were continuation of medication with ICU-only indication (28.4%), untreated condition (19.4%), and pharmacotherapy without indication (11.9%). Seventy-five percent of errors reached the patient but did not cause harm. The occurrence of errors varied by type and size of institution and ICU. Renal replacement therapy during ICU stay and number of medications ordered following transfer were identified as factors associated with occurrence of error (odds ratio, 2.93; 95% CI, 1.42–6.05; odds ratio 1.08, 95% CI, 1.02–1.14, respectively). Orders for anti-infective (odds ratio, 1.66; 95% CI, 1.19–2.32), hematologic agents (1.75; 95% CI, 1.17–2.62), and IV fluids, electrolytes, or diuretics (odds ratio, 1.73; 95% CI, 1.21–2.48) at transition of care were associated with an increased odds of error. Factors associated with decreased odds of error included daily patient care rounds in the ICU (odds ratio, 0.15; 95% CI, 0.07–0.34) and orders discontinued and rewritten at the time of transfer from the ICU (odds ratio, 0.36; 95% CI, 0.17–0.73). 
Conclusions: Nearly half of patients experienced medication errors at the time of transition of care from an ICU to non-ICU location. Most errors reached the patient but did not cause harm. This study identified risk factors upon which risk mitigation strategies should be focused.

A Fate Worse Than Death: Prognostication of Devastating Brain Injury

by Pratt, Alexandra K.; Chang, Jason J.; Sederstrom, Nneka O.  

Objectives: To describe the sources of uncertainty in prognosticating devastating brain injury, the role of the intensivist in prognostication, and ethical considerations in prognosticating devastating brain injury in the ICU.
Data Sources: A PubMed literature review was performed.
Study Selection: Articles relevant to prognosis in intracerebral hemorrhage, acute ischemic stroke, traumatic brain injury, subarachnoid hemorrhage, and postcardiac arrest anoxic encephalopathy were selected.
Data Extraction: Data regarding definition and prognosis of devastating brain injury were extracted. Themes related to how clinicians perform prognostication and their accuracy were reviewed and extracted.
Data Synthesis: Although there are differences in pathophysiology and therefore prognosis in the various etiologies of devastating brain injury, some common themes emerge. Physicians tend to have fairly good prognostic accuracy, especially in severe cases with poor prognosis. Full supportive care is recommended for at least 72 hours from initial presentation to maximize the potential for recovery and minimize secondary injury. However, physician approaches to the timing of and recommendations for withdrawal of life-sustaining therapy have a significant impact on mortality from devastating brain injury.
Conclusions: Intensivists should consider the modern literature describing prognosis for devastating brain injury and provide appropriate time for patient recovery and for discussions with the patient’s surrogates. Surrogates wish to have a prognosis enumerated even when uncertainty exists. These discussions must be handled with care and include admission of uncertainty when it exists. Respect for patient autonomy remains paramount, although physicians are not required to provide inappropriate medical therapies.

Incidence, Risk Factors, and Outcomes of Intra-Abdominal Hypertension in Critically Ill Patients—A Prospective Multicenter Study (IROI Study)

by Reintam Blaser, Annika; Regli, Adrian; De Keulenaer, Bart; Kimball, Edward J.; Starkopf, Liis; Davis, Wendy A.; Greiffenstein, Patrick; Starkopf, Joel; the Incidence, Risk Factors, and Outcomes of Intra-Abdominal (IROI) Study Investigators  

Objectives: To identify the prevalence, risk factors, and outcomes of intra-abdominal hypertension in a mixed multicenter ICU population.
Design: Prospective observational study.
Setting: Fifteen ICUs worldwide.
Patients: Consecutive adult ICU patients with a bladder catheter. Interventions: None. Measurements and Main Results: Four hundred ninety-one patients were included. Intra-abdominal pressure was measured a minimum of every 8 hours. Subjects with a mean intra-abdominal pressure equal to or greater than 12 mm Hg were defined as having intra-abdominal hypertension. Intra-abdominal hypertension was present in 34.0% of the patients on the day of ICU admission (159/467) and in 48.9% of the patients (240/491) during the observation period. The severity of intra-abdominal hypertension was as follows: grade I, 47.5%; grade II, 36.6%; grade III, 11.7%; and grade IV, 4.2%. The severity of intra-abdominal hypertension during the first 2 weeks of the ICU stay was identified as an independent predictor of 28- and 90-day mortality, whereas the presence of intra-abdominal hypertension on the day of ICU admission did not predict mortality. Body mass index, Acute Physiology and Chronic Health Evaluation II score greater than or equal to 18, presence of abdominal distension, absence of bowel sounds, and positive end-expiratory pressure greater than or equal to 7 cm H2O were independently associated with the development of intra-abdominal hypertension at any time during the observation period. In subjects without intra-abdominal hypertension on day 1, body mass index combined with daily positive fluid balance and positive end-expiratory pressure greater than or equal to 7 cm H2O (as documented on the day before intra-abdominal hypertension occurred) were associated with the development of intra-abdominal hypertension during the first week in the ICU.
Conclusions: In our mixed ICU patient cohort, intra-abdominal hypertension occurred in almost half of all subjects and was twice as prevalent in mechanically ventilated patients as in spontaneously breathing patients. Presence and severity of intra-abdominal hypertension during the observation period significantly and independently increased 28- and 90-day mortality. Five admission day variables were independently associated with the presence or development of intra-abdominal hypertension. Positive fluid balance was associated with the development of intra-abdominal hypertension after day 1.

Treatment With Acetylsalicylic Acid Reverses Endotoxin Tolerance in Humans In Vivo: A Randomized Placebo-Controlled Study

by Leijte, Guus P.; Kiers, Dorien; van der Heijden, Wouter; Jansen, Aron; Gerretsen, Jelle; Boerrigter, Verin; Netea, Mihai G.; Kox, Matthijs; Pickkers, Peter  

Objective: To investigate immunostimulatory effects of acetylsalicylic acid during experimental human endotoxemia and in sepsis patients.
Design: Double-blind, randomized, placebo-controlled study in healthy volunteers and ex vivo stimulation experiments using monocytes of septic patients.
Setting: Intensive care research unit of an university hospital.
Subjects: Thirty healthy male volunteers and four sepsis patients. Interventions: Healthy volunteers were challenged IV with endotoxin twice, at a 1-week interval, with each challenge consisting of a bolus of 1 ng/kg followed by continuous administration of 1 ng/kg/hr during 3 hours. Volunteers were randomized to acetylsalicylic acid prophylaxis (80 mg acetylsalicylic acid daily for a 14-d period, starting 7 d before the first endotoxin challenge), acetylsalicylic acid treatment (80 mg acetylsalicylic acid daily for the 7-d period in-between both endotoxin challenges), or the control group (receiving placebo). Furthermore, monocytes of sepsis patients were incubated with acetylsalicylic acid preexposed platelets and were subsequently stimulated with endotoxin.
Measurements and Main Results: Acetylsalicylic acid prophylaxis enhanced plasma tumor necrosis factor-α concentrations upon the first endotoxin challenge by 50% compared with the control group (p = 0.02) but did not modulate cytokine responses during the second endotoxin challenge. In contrast, acetylsalicylic acid treatment resulted in enhanced plasma levels of tumor necrosis factor-α (+53%; p = 0.02), interleukin-6 (+91%; p = 0.03), and interleukin-8 (+42%; p = 0.02) upon the second challenge, whereas plasma levels of the key antiinflammatory cytokine interleukin-10 were attenuated (–40%; p = 0.003). This proinflammatory phenotype in the acetylsalicylic acid treatment group was accompanied by a decrease in urinary prostaglandin E metabolite levels (–27% ± 7%; p = 0.01). Ex vivo exposure of platelets to acetylsalicylic acid increased production of tumor necrosis factor-α (+66%) and decreased production of interleukin-10 (–23%) by monocytes of sepsis patients. Conclusions: Treatment, but not prophylaxis, with low-dose acetylsalicylic acid, partially reverses endotoxin tolerance in humans in vivo by shifting response toward a proinflammatory phenotype. This acetylsalicylic acid–induced proinflammatory shift was also observed in septic monocytes, signifying that patients suffering from sepsis-induced immunoparalysis might benefit from initiating acetylsalicylic acid treatment.

Variation in Identifying Sepsis and Organ Dysfunction Using Administrative Versus Electronic Clinical Data and Impact on Hospital Outcome Comparisons*

by Rhee, Chanu; Jentzsch, Maximilian S.; Kadri, Sameer S.; Seymour, Christopher W.; Angus, Derek C.; Murphy, David J.; Martin, Greg S.; Dantes, Raymund B.; Epstein, Lauren; Fiore, Anthony E.; Jernigan, John A.; Danner, Robert L.; Warren, David K.; Septimus, Edward J.; Hickok, Jason; Poland, Russell E.; Jin, Robert; Fram, David; Schaaf, Richard; Wang, Rui; Klompas, Michael; for the Centers for Disease Control and Prevention (CDC) Prevention Epicenters Program  

Objectives: Administrative claims data are commonly used for sepsis surveillance, research, and quality improvement. However, variations in diagnosis, documentation, and coding practices for sepsis and organ dysfunction may confound efforts to estimate sepsis rates, compare outcomes, and perform risk adjustment. We evaluated hospital variation in the sensitivity of claims data relative to clinical data from electronic health records and its impact on outcome comparisons.
Design, Setting, and Patients: Retrospective cohort study of 4.3 million adult encounters at 193 U.S. hospitals in 2013–2014.
Interventions: None.
Measurements and Main Results: Sepsis was defined using electronic health record–derived clinical indicators of presumed infection (blood culture draws and antibiotic administrations) and concurrent organ dysfunction (vasopressors, mechanical ventilation, doubling in creatinine, doubling in bilirubin to ≥ 2.0 mg/dL, decrease in platelets to < 100 cells/µL, or lactate ≥ 2.0 mmol/L). We compared claims for sepsis prevalence and mortality rates between both methods. All estimates were reliability adjusted to account for random variation using hierarchical logistic regression modeling. The sensitivity of hospitals’ claims data was low and variable: median 30% (range, 5–54%) for sepsis, 66% (range, 26–84%) for acute kidney injury, 39% (range, 16–60%) for thrombocytopenia, 36% (range, 29–44%) for hepatic injury, and 66% (range, 29–84%) for shock. Correlation between claims and clinical data was moderate for sepsis prevalence (Pearson coefficient, 0.64) and mortality (0.61). Among hospitals in the lowest sepsis mortality quartile by claims, 46% shifted to higher mortality quartiles using clinical data. Using implicit sepsis criteria based on infection and organ dysfunction codes also yielded major differences versus clinical data.
Conclusions: Variation in the accuracy of claims data for identifying sepsis and organ dysfunction limits their use for comparing hospitals’ sepsis rates and outcomes. Using objective clinical data may facilitate more meaningful hospital comparisons.