Waveform Morphology as a Surrogate for ICP Monitoring: A Comparison Between an Invasive and a Noninvasive Method.

BACKGROUND: Although the placement of an intraventricular catheter remains the gold standard technique for measuring intracranial pressure (ICP), the method has several limitations. Therefore, noninvasive alternatives to ICP (ICPni) measurement are of great interest. The main objective of this study was to compare the correlation and agreement of wave morphology between ICP (standard intraventricular ICP monitoring) and a new ICPni monitor in patients admitted with stroke. The second objective was to estimate the discrimination of the noninvasive method to detect intracranial hypertension. METHODS: We prospectively collected data of adults admitted to an intensive care unit with subarachnoid hemorrhage, intracerebral hemorrhage, or ischemic stroke in whom an invasive ICP monitor was placed. Measurements were simultaneously collected from two parameters [time-to-peak (TTP) and the ratio regarding the second and first peak of the ICP wave (P2/P1 ratio)] of ICP and ICPni wave morphology monitors (Brain4care). Intracranial hypertension was defined as an invasively measured sustained ICP > 20 mm Hg for at least 5 min. RESULTS: We studied 18 patients (subarachnoid hemorrhage = 14; intracerebral hemorrhage = 3; ischemic stroke = 1) on 60 occasions with a median age of 52 ± 14.3 years. A total of 197,400 waves (2495 min) from both ICP (standard ICP monitoring) and the ICPni monitor were sliced into 1-min-long segments, and we determined TTP and the P2/P1 ratio from the mean pulse. The median invasively measured ICP was 13 (9.8-16.2) mm Hg, and intracranial hypertension was present on 18 occasions (30%). The correlation and agreement between invasive and noninvasive methods for wave morphology were strong for the P2/P1 ratio and moderate for TTP using categoric (κ agreement 88.1% and 71.3%, respectively) and continuous (intraclass correlation coefficient 0.831 and 0.584, respectively) measures. There was a moderate but significant correlation with the mean ICP value (P2/P1 ratio r = 0.427; TTP r = 0.353; p < 0.001 for all) between noninvasive and invasive techniques. The areas under the curve to estimate intracranial hypertension were 0.786 [95% confidence interval (CI) 0.72-0.93] for the P2/P1 ratio and 0.694 (95% CI 0.60-0.74) for TTP. CONCLUSIONS: The new ICPni wave morphology monitor showed a good agreement with the standard invasive method and an acceptable discriminatory power to detect intracranial hypertension. Clinical trial registration Trial registration: NCT05121155.

Sepsis in patients hospitalized with coronavirus disease 2019: how often and how severe?

PURPOSE OF REVIEW: To discuss why severe COVID-19 should be considered sepsis and how co-infection and secondary infection can aggravate this condition and perpetuate organ dysfunction leading to high mortality rates. RECENT FINDINGS: In severe COVID-19, there is both direct viral toxicity and dysregulated host response to infection. Although both coinfection and/or secondary infection are present, the latest is of greater concern mainly in resource-poor settings. Patients with severe COVID-19 present a phenotype of multiorgan dysfunction that leads to death in an unacceptable high percentage of the patients, with wide variability around the world. Similarly to endemic sepsis, the mortality of COVID-19 critically ill patients is higher in low-income and middle-income countries as compared with high-income countries. Disparities, including hospital strain, resources limitations, higher incidence of healthcare-associated infections (HAI), and staffing issues could in part explain this variability. SUMMARY: The high mortality rates of critically ill patients with severe COVID-19 disease are not only related to the severity of patient disease but also to modifiable factors, such as the ICU strain, HAI incidence, and organizational aspects. Therefore, HAI prevention and the delivery of best evidence-based care for these patients to avoid additional damage is important. Quality improvement interventions might help in improving outcomes mainly in resource-limited settings.

Efficacy and Safety of a Nasopharyngeal Catheter for Selective Brain Cooling in Patients with Traumatic Brain Injury: A Prospective, Non-randomized Pilot Study.

BACKGROUND: The efficacy objective was to determine whether a novel nasopharyngeal catheter could be used to cool the human brain after traumatic brain injury, and the safety objective was to assess the local and systemic effects of this therapeutic strategy. METHODS: This was a prospective, non-randomized, interventional clinical trial that involved five patients with severe traumatic brain injury. The intervention consisted of inducing and maintaining selective brain cooling for 24 h by positioning a catheter in the nasopharynx and circulating cold water inside the catheter in a closed-loop arrangement. Core temperature was maintained at ≥ 35 °C using counter-warming. RESULTS: In all study participants, a brain temperature reduction of ≥ 2 °C was achieved. The mean brain temperature reduction from baseline was 2.5 ± 0.9 °C (P = .04, 95% confidence interval). The mean systemic temperature was 37.3 ± 1.1 °C at baseline and 36.0 ± 0.8 °C during the intervention. The mean difference between the brain temperature and the systemic temperature during intervention was - 1.2 ± 0.8 °C (P = .04). The intervention was well tolerated with no significant changes observed in the hemodynamic parameters. No relevant variations in intracranial pressure and transcranial Doppler were observed. The laboratory results underwent no major changes, aside from the K+ levels and blood counts. The K+ levels significantly varied (P = .04); however, the variation was within the normal range. Only one patient experienced an event of mild localized and superficial nasal discoloration, which was re-evaluated on the seventh day and indicated complete recovery. CONCLUSION: The results suggest that our noninvasive method for selective brain cooling, using a novel nasopharyngeal catheter, was effective and safe for use in humans.

Effect of Increasing Blood Pressure With Noradrenaline on the Microcirculation of Patients With Septic Shock and Previous Arterial Hypertension.

OBJECTIVES: To assess whether an increase in mean arterial pressure in patients with septic shock and previous systemic arterial hypertension changes microcirculatory and systemic hemodynamic variables compared with patients without arterial hypertension (control). DESIGN: Prospective, nonblinded, interventional study. SETTING: Three ICUs in two teaching hospitals. PATIENTS: After informed consent, we included patients older than 18 years with septic shock for at least 6 hours, sedated, and under mechanical ventilation. We paired patients with and without arterial hypertension by age. INTERVENTIONS: After obtaining systemic and microcirculation baseline hemodynamic variables (time 0), we increased noradrenaline dose to elevate mean arterial pressure up to 85-90 mm Hg before collecting a new set of measurements (time 1). MEASUREMENTS AND MAIN RESULTS: We included 40 patients (20 in each group). There was no significant difference in age between the groups. After the rise in mean arterial pressure, there was a significant increase in cardiac index and a slight but significant reduction in lactate in both groups. We observed a significant improvement in the proportion of perfused vessels (control: 57.2 ± 14% to 66 ± 14.8%; arterial hypertension: 61.4 ± 12.3% to 70.8 ± 7.1%; groups: p = 0.29; T0 and T1: p < 0.001; group and time interaction: p = 0.85); perfused vessels density (control: 15.6 ± 4 mm/mm to 18.6 ± 4.5 mm/mm; arterial hypertension: 16.4 ± 3.5 mm/mm to 19.1 ± 3 mm/mm; groups: p = 0.51; T0 and T1: p < 0.001; group and time interaction: p = 0.70), and microcirculatory flow index (control: 2.1 ± 0.6 to 2.4 ± 0.6; arterial hypertension: 2.1 ± 0.5 to 2.6 ± 0.2; groups: p = 0.71; T0 and T1: p = 0.002; group and time interaction: p = 0.45) in both groups. CONCLUSIONS: Increasing mean arterial pressure with noradrenaline in septic shock patients improves density and flow in small vessels of sublingual microcirculation. However, this improvement occurs both in patients with previous arterial hypertension and in those without arterial hypertension.

Clinical Features of Kidney Transplant Recipients Admitted to the Intensive Care Unit.

INTRODUCTION: There is a paucity of data regarding the complications in kidney transplant patients who may require intensive care unit (ICU) management, despite being the most common solid organ transplant worldwide. OBJECTIVE: To identify the main reasons for ICU admission and to determine the factors associated with hospital mortality in kidney transplant recipients. DESIGN: This single-center retrospective cohort study was conducted between September 2013 and June 2014, including all consecutive kidney transplant patients requiring ICU admission. We collected data on patient demographics, transplant characteristics, clinical data, and prognostic scores. The independent determinants of hospital mortality were identified by multiple logistic regression analysis. We also assessed the performance of Simplified Acute Physiology Score 3 (SAPS 3) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. RESULTS: We analyzed data from 413 patients, the majority of whom were admitted late after renal transplantation (1169 days; 63-3003 days). The main reason for admission was sepsis (33.2%), followed by cardiovascular disease (16%). Age (odds ratio [OR] 1.05, confidence interval [CI], 1.01-1.09), SAPS 3 score (OR 1.04, CI, 1.01-1.08), the need for mechanical ventilation (OR 26.47, CI, 10.30-68.08), and vasopressor use (OR 3.34, CI, 1.37-8.13) were independently associated with hospital mortality. The performance of SAPS 3 and APACHE II scores was poor in this population and overestimated the mortality rates. CONCLUSION: Sepsis was the main reason for ICU admission in kidney transplant recipients, followed by cardiovascular disease. Age and disease severity were associated with hospital mortality.

Assessment of the components of fluid balance in patients with septic shock: a prospective observational study.

BACKGROUND: The optimal amount for initial fluid resuscitation is still controversial in sepsis and the contribution of non-resuscitation fluids in fluid balance is unclear. We aimed to investigate the main components of fluid intake and fluid balance in both survivors and non-survivor patients with septic shock within the first 72 hours. METHODS: In this prospective observational study in two intensive care units, we recorded all fluids administered intravenously, orally, or enterally, and losses during specific time intervals from vasopressor initiation: T1 (up to 24 hours), T2 (24 to 48 hours) and T3 (48 to 72 hours). Logistic regression and a mathematical model assessed the association with mortality and the influence of severity of illness. RESULTS: We included 139 patients. The main components of fluid intake varied across different time intervals, with resuscitation and non-resuscitation fluids such as antimicrobials and maintenance fluids being significant contributors in T1 and nutritional therapy in T2/T3. A positive fluid balance both in T1 and T2 was associated with mortality (p = 0.049; p = 0.003), while nutritional support in T2 was associated with lower mortality (p = 0.040). The association with mortality was not explained by severity of illness scores. CONCLUSIONS: Non-resuscitation fluids are major contributors to a positive fluid balance within the first 48 hours of resuscitation. A positive fluid balance in the first 24 and 48 hours seems to independently increase the risk of death, while higher amount of nutrition seems protective. This data might inform fluid stewardship strategies aiming to improve outcomes and minimize complications in sepsis.

Multimodal monitoring intracranial pressure by invasive and noninvasive means.

Although the placement of an intraventricular catheter remains the gold standard method for the diagnosis of intracranial hypertension (ICH), the technique has several limitations including but not limited to its invasiveness. Current noninvasive methods, however, still lack robust evidence to support their clinical use. We aimed to estimate, as an exploratory hypothesis generating analysis, the discriminative power of four noninvasive methods to diagnose ICH. We prospectively collected data from adult intensive care unit (ICU) patients with subarachnoid hemorrhage (SAH), intraparenchymal hemorrhage (IPH), and ischemic stroke (IS) in whom invasive intracranial pressure (ICP) monitoring had been placed. Measures were simultaneously collected from the following noninvasive methods: optic nerve sheath diameter (ONSD), pulsatility index (PI) using transcranial Doppler (TCD), a 5-point visual scale designed for brain Computed Tomography (CT), and two parameters (time-to-peak [TTP] and P2/P1 ratio) of a noninvasive ICP wave morphology monitor (Brain4Care[B4c]). ICH was defined as a sustained ICP > 20 mmHg for at least 5 min. We studied 18 patients (SAH = 14; ICH = 3; IS = 1) on 60 occasions with a mean age of 52 ± 14.3 years. All methods were recorded simultaneously, except for the CT, which was performed within 24 h of the other methods. The median ICP was 13 [9.8-16.2] mmHg, and intracranial hypertension was present on 18 occasions (30%). Median values from the noninvasive techniques were ONSD 4.9 [4.40-5.41] mm, PI 1.22 [1.04-1.43], CT scale 3 points [IQR: 3.0], P2/P1 ratio 1.16 [1.09-1.23], and TTP 0.215 [0.193-0.237]. There was a significant statistical correlation between all the noninvasive techniques and invasive ICP (ONSD, r = 0.29; PI, r = 0.62; CT, r = 0.21; P2/P1 ratio, r = 0.35; TTP, r = 0.35, p < 0.001 for all comparisons). The area under the curve (AUC) to estimate intracranial hypertension was 0.69 [CIs = 0.62-0.78] for the ONSD, 0.75 [95% CIs 0.69-0.83] for the PI, 0.64 [95%Cis 0.59-069] for CT, 0.79 [95% CIs 0.72-0.93] for P2/P1 ratio, and 0.69 [95% CIs 0.60-0.74] for TTP. When the various techniques were combined, an AUC of 0.86 [0.76-0.93]) was obtained. The best pair of methods was the TCD and B4cth an AUC of 0.80 (0.72-0.88). Noninvasive technique measurements correlate with ICP and have an acceptable discrimination ability in diagnosing ICH. The multimodal combination of PI (TCD) and wave morphology monitor may improve the ability of the noninvasive methods to diagnose ICH. The observed variability in non-invasive ICP estimations underscores the need for comprehensive investigations to elucidate the optimal method-application alignment across distinct clinical scenarios.

Effects of balanced solution on short-term outcomes in traumatic brain injury patients: a secondary analysis of the BaSICS randomized trial. / Efeitos da solução balanceada em desfechos de curto prazo em pacientes com traumatismo craniencefálico: uma análise secundária do ensaio clínico randomizado BaSICS.

OBJECTIVE: To describe the effects of balanced solution use on the short-term outcomes of patients with traumatic brain injury enrolled in BaSICS trial. METHODS: Patients were randomized to receive either 0.9% saline or balanced solution during their intensive care unit stay. The primary endpoint was 90-day mortality, and the secondary outcomes were days alive and free of intensive care unit stay at 28 days. The primary endpoint was assessed using Bayesian logistic regression. The secondary endpoint was assessed using a Bayesian zero-inflated beta binomial regression. RESULTS: We included 483 patients (236 in the 0.9% saline arm and 247 in the balanced solution arm). A total of 338 patients (70%) with a Glasgow coma scale score ≤ 12 were enrolled. The overall probability that balanced solutions were associated with higher 90-day mortality was 0.98 (OR 1.48; 95%CrI 1.04 - 2.09); this mortality increment was particularly noticeable in patients with a Glasgow coma scale score below 6 at enrollment (probability of harm of 0.99). Balanced solutions were associated with -1.64 days alive and free of intensive care unit at 28 days (95%CrI -3.32 - 0.00) with a probability of harm of 0.97. CONCLUSION: There was a high probability that balanced solutions were associated with high 90-day mortality and fewer days alive and free of intensive care units at 28 days.ClinicalTrials.gov: NCT02875873.

OBJETIVO: Descrever os efeitos do uso de soluções balanceadas nos desfechos de curto prazo de pacientes com traumatismo craniencefálico incluídos no estudo BaSICS. MÉTODOS: Os pacientes foram randomizados para receber solução salina 0,9% ou solução balanceada durante a internação em unidade de terapia intensiva. O desfecho primário foi mortalidade em 90 dias, já os desfechos secundários foram dias de vida e sem internação em unidade de terapia intensiva aos 28 dias. O desfecho primário foi avaliado por regressão logística bayesiana. O desfecho secundário foi avaliado usando regressão beta-binomial inflada de zeros bayesiana. RESULTADOS: Incluímos 483 pacientes (236 no braço de solução salina 0,9% e 247 no braço de solução balanceada). Foram incluídos 338 pacientes (70%) com pontuação na escala de coma de Glasgow ≤ 12. A probabilidade geral de que soluções balanceadas estivessem associadas a maior mortalidade em 90 dias foi de 0,98 (RC de 1,48; ICr95% 1,04 - 2,09). Esse aumento de mortalidade foi particularmente perceptível em pacientes com pontuação na escala de coma de Glasgow abaixo de 6 no momento da inclusão (probabilidade de dano de 0,99). Soluções balanceadas foram associadas a -1,64 dia de vida e sem internação em unidade de terapia intensiva aos 28 dias (ICr95% -3,32 - 0,00) com probabilidade de dano de 0,97. CONCLUSÃO: Houve alta probabilidade de que soluções balanceadas estivessem associadas a alta mortalidade em 90 dias, menos dias de vida e sem internação em unidade de terapia intensiva aos 28 dias.ClinicalTrials.gov: NCT02875873.

Resuscitation fluid practices in Brazilian intensive care units: a secondary analysis of Fluid-TRIPS. / Práticas de ressuscitação volêmica em unidades de terapia intensiva brasileiras: uma análise secundária do estudo Fluid-TRIPS.

OBJECTIVE: To describe fluid resuscitation practices in Brazilian intensive care units and to compare them with those of other countries participating in the Fluid-TRIPS. METHODS: This was a prospective, international, cross-sectional, observational study in a convenience sample of intensive care units in 27 countries (including Brazil) using the Fluid-TRIPS database compiled in 2014. We described the patterns of fluid resuscitation use in Brazil compared with those in other countries and identified the factors associated with fluid choice. RESULTS: On the study day, 3,214 patients in Brazil and 3,493 patients in other countries were included, of whom 16.1% and 26.8% (p < 0.001) received fluids, respectively. The main indication for fluid resuscitation was impaired perfusion and/or low cardiac output (Brazil: 71.7% versus other countries: 56.4%, p < 0.001). In Brazil, the percentage of patients receiving crystalloid solutions was higher (97.7% versus 76.8%, p < 0.001), and 0.9% sodium chloride was the most commonly used crystalloid (62.5% versus 27.1%, p < 0.001). The multivariable analysis suggested that the albumin levels were associated with the use of both crystalloids and colloids, whereas the type of fluid prescriber was associated with crystalloid use only. CONCLUSION: Our results suggest that crystalloids are more frequently used than colloids for fluid resuscitation in Brazil, and this discrepancy in frequencies is higher than that in other countries. Sodium chloride (0.9%) was the crystalloid most commonly prescribed. Serum albumin levels and the type of fluid prescriber were the factors associated with the choice of crystalloids or colloids for fluid resuscitation.

OBJETIVO: Descrever as práticas de ressuscitação volêmica em unidades de terapia intensiva brasileiras e compará-las com as de outros países participantes do estudo Fluid-TRIPS. MÉTODOS: Este foi um estudo observacional transversal, prospectivo e internacional, de uma amostra de conveniência de unidades de terapia intensiva de 27 países (inclusive o Brasil), com utilização da base de dados Fluid-TRIPS compilada em 2014. Descrevemos os padrões de ressuscitação volêmica utilizados no Brasil em comparação com os de outros países e identificamos os fatores associados com a escolha dos fluidos. RESULTADOS: No dia do estudo, foram incluídos 3.214 pacientes do Brasil e 3.493 pacientes de outros países, dos quais, respectivamente, 16,1% e 26,8% (p < 0,001) receberam fluidos. A principal indicação para ressuscitação volêmica foi comprometimento da perfusão e/ou baixo débito cardíaco (Brasil 71,7% versus outros países 56,4%; p < 0,001). No Brasil, a percentagem de pacientes que receberam soluções cristaloides foi mais elevada (97,7% versus 76,8%; p < 0,001), e solução de cloreto de sódio a 0,9% foi o cristaloide mais comumente utilizado (62,5% versus 27,1%; p < 0,001). A análise multivariada sugeriu que os níveis de albumina se associaram com o uso tanto de cristaloides quanto de coloides, enquanto o tipo de prescritor dos fluidos se associou apenas com o uso de cristaloides. CONCLUSÃO: Nossos resultados sugerem que cristaloides são usados mais frequentemente do que coloides para ressuscitação no Brasil, e essa discrepância, em termos de frequências, é mais elevada do que em outros países. A solução de cloreto de sódio 0,9% foi o cristaloide mais frequentemente prescrito. Os níveis de albumina sérica e o tipo de prescritor de fluidos foram os fatores associados com a escolha de cristaloides ou coloides para a prescrição de fluidos.

Statistical analysis plan for the Balanced Solution versus Saline in Intensive Care Study (BaSICS). / Plano de análise estatística para o estudo Balanced Solution versus Saline in Intensive Care Study (BaSICS).

OBJECTIVE: To report the statistical analysis plan (first version) for the Balanced Solutions versus Saline in Intensive Care Study (BaSICS). METHODS: BaSICS is a multicenter factorial randomized controlled trial that will assess the effects of Plasma-Lyte 148 versus 0.9% saline as the fluid of choice in critically ill patients, as well as the effects of a slow (333mL/h) versus rapid (999mL/h) infusion speed during fluid challenges, on important patient outcomes. The fluid type will be blinded for investigators, patients and the analyses. No blinding will be possible for the infusion speed for the investigators, but all analyses will be kept blinded during the analysis procedure. RESULTS: BaSICS will have 90-day mortality as its primary endpoint, which will be tested using mixed-effects Cox proportional hazard models, considering sites as a random variable (frailty models) adjusted for age, organ dysfunction and admission type. Important secondary endpoints include renal replacement therapy up to 90 days, acute renal failure, organ dysfunction at days 3 and 7, and mechanical ventilation-free days within 28 days. CONCLUSION: This manuscript provides details on the first version of the statistical analysis plan for the BaSICS trial and will guide the study's analysis when follow-up is finished.

OBJETIVO: Relatar o plano de análise estatística (primeira versão) para o estudo Balanced Solutions versus Saline in Intensive Care Study (BaSICS). MÉTODOS: O estudo BaSICS é um ensaio multicêntrico fatorial e randomizado que avaliará os efeitos da administração dos fluidos Plasma-Lyte 148 em comparação com solução salina 0,9% como fluido de escolha em pacientes críticos, assim como os efeitos de uma velocidade de infusão lenta (333mL/hora) em comparação com uma velocidade de infusão rápida (999mL/hora) durante desafios com volume, em importantes desfechos do paciente. O tipo de fluido será mantido cego para os investigadores, pacientes e nas análises. Não será possível, entretanto, ocultar dos investigadores a velocidade de infusão, mas os procedimentos de análise serão mantidos cegos quanto a esse aspecto. RESULTADOS: O estudo BaSICS terá como parâmetro primário a mortalidade em 90 dias, que será testada com utilização de modelos de risco proporcional de Cox de efeitos mistos, considerando os centros de estudo como variável randômica (modelos de fragilidade) ajustada por idade, disfunção de órgãos e tipo de admissão. Os parâmetros secundários importantes incluem terapia de substituição renal até 90 dias, insuficiência renal aguda, disfunção de órgãos nos dias 3 e 7 e dias sem ventilação mecânica em 28 dias. CONCLUSÃO: Este artigo fornece detalhes referentes à primeira versão do plano de análise estatística para o estudo BaSICS e orientará a análise do estudo após a conclusão do seguimento.

Elderly patients with cancer admitted to intensive care unit: A multicenter study in a middle-income country.

BACKGROUND: Very elderly critically ill patients (ie, those older than 75 or 80 years) are an increasing population in intensive care units. However, patients with cancer have encompassed only a minority in epidemiological studies of very old critically-ill patients. We aimed to describe clinical characteristics and identify factors associated with hospital mortality in a cohort of patients aged 80 or older with cancer admitted to intensive care units (ICUs). METHODS: This was a retrospective cohort study in 94 ICUs in Brazil. We included patients aged 80 years or older with active cancer who had an unplanned admission. We performed a mixed effect logistic regression model to identify variables independently associated with hospital mortality. RESULTS: Of 4604 included patients, 1807 (39.2%) died in hospital. Solid metastatic (OR = 2.46; CI 95%, 2.01-3.00), hematological cancer (OR = 2.32; CI 95%, 1.75-3.09), moderate/severe performance status impairment (OR = 1.59; CI 95%, 1.33-1.90) and use of vasopressors (OR = 4.74; CI 95%, 3.88-5.79), mechanical ventilation (OR = 1.54; CI 95%, 1.25-1.89) and renal replacement (OR = 1.81; CI 95%, 1.29-2.55) therapy were independently associated with increased hospital mortality. Emergency surgical admissions were associated with lower mortality compared to medical admissions (OR = 0.71; CI 95%, 0.52-0.96). CONCLUSIONS: Hospital mortality rate in very elderly critically ill patients with cancer with unplanned ICU admissions are lower than expected a priori. Cancer characteristics, performance status impairment and acute organ dysfunctions are associated with increased mortality.

Assessment of the components of fluid balance in patients with septic shock: a prospective observational study

Abstract Background: The optimal amount for initial fluid resuscitation is still controversial in sepsis and the contribution of non-resuscitation fluids in fluid balance is unclear. We aimed to investigate the main components of fluid intake and fluid balance in both survivors and non-survivor patients with septic shock within the first 72 hours. Methods: In this prospective observational study in two intensive care units, we recorded all fluids administered intravenously, orally, or enterally, and losses during specific time intervals from vasopressor initiation: T1 (up to 24 hours), T2 (24 to 48 hours) and T3 (48 to 72 hours). Logistic regression and a mathematical model assessed the association with mortality and the influence of severity of illness. Results: We included 139 patients. The main components of fluid intake varied across different time intervals, with resuscitation and non-resuscitation fluids such as antimicrobials and maintenance fluids being significant contributors in T1 and nutritional therapy in T2/T3. A positive fluid balance both in T1 and T2 was associated with mortality (p = 0.049; p = 0.003), while nutritional support in T2 was associated with lower mortality (p = 0.040). The association with mortality was not explained by severity of illness scores. Conclusions: Non-resuscitation fluids are major contributors to a positive fluid balance within the first 48 hours of resuscitation. A positive fluid balance in the first 24 and 48 hours seems to independently increase the risk of death, while higher amount of nutrition seems protective. This data might inform fluid stewardship strategies aiming to improve outcomes and minimize complications in sepsis.

Sepsis in Solid-Organ Transplant Patients.

The growing population of solid organ transplant (SOT) recipients is at a significantly increased risk for developing infections. In some patients, the infection can lead to a dysregulated systemic inflammatory response with acute organ dysfunction. SOT recipients with sepsis tend to have less fever and leukocytosis instances. Moreover, they have diminished symptoms and attenuated clinical and radiologic findings. The current management of sepsis is similar to general patients. It relies mainly on early recognition and treatment, including appropriate administration of antibiotics and resuscitation with intravenous fluids and vasoactive drugs when needed. The infusion of fluids should be closely monitored because elevated central venous pressure levels and fluid overload can be particularly harmful. There is no consensus on how to manage immunosuppressive therapies during sepsis, although dose reduction or withdrawal is suggested to improve the host immunological response. There is compelling evidence suggesting that infections are associated with reduced allograft and patient survival. However, the traditional belief that SOT patients who develop sepsis have worse outcomes than non-transplanted patients has been challenged.

Short-term effects of passive mobilization on the sublingual microcirculation and on the systemic circulation in patients with septic shock.

BACKGROUND: Active mobilization is not possible in patients under deep sedation and unable to follow commands. In this scenario, passive therapy is an interesting alternative. However, in patients with septic shock, passive mobilization may have risks related to increased oxygen consumption. Our objective was to evaluate the impact of passive mobilization on sublingual microcirculation and systemic hemodynamics in patients with septic shock. METHODS: We included patients who were older than 18 years, who presented with septic shock, and who were under sedation and mechanical ventilation. Passive exercise was applied for 20 min with 30 repetitions per minute. Systemic hemodynamic and microcirculatory variables were compared before (T0) and up to 10 min after (T1) passive exercise. p values <0.05 were considered significant. RESULTS: We included 35 patients (median age [IQR 25-75%]: 68 [49.0-78.0] years; mean (±SD) Simplified Acute Physiologic Score (SAPS) 3 score: 66.7 ± 12.1; median [IQR 25-75%] Sequential Organ Failure Assessment (SOFA) score: 9 [7.0-12.0]). After passive mobilization, there was a slight but significant increase in proportion of perfused vessels (PPV) (T0 [IQR 25-75%]: 78.2 [70.9-81.9%]; T1 [IQR 25-75%]: 80.0 [75.2-85.1] %; p = 0.029), without any change in other microcirculatory variables. There was a reduction in heart rate (HR) (T0 (mean ± SD): 95.6 ± 22.0 bpm; T1 (mean ± SD): 93.8 ± 22.0 bpm; p < 0.040) and body temperature (T0 (mean ± SD): 36.9 ± 1.1 °C; T1 (mean ± SD): 36.7 ± 1.2 °C; p < 0.002) with no change in other systemic hemodynamic variables. There was no significant correlation between PPV variation and HR (r = -0.010, p = 0.955), cardiac index (r = 0.218, p = 0.215) or mean arterial pressure (r = 0.276, p = 0.109) variation. CONCLUSIONS: In patients with septic shock after the initial phase of hemodynamic resuscitation, passive exercise is not associated with relevant changes in sublingual microcirculation or systemic hemodynamics.

[Effects of the positive end-expiratory pressure increase on sublingual microcirculation in patients with acute respiratory distress syndrome]. / Efeitos do aumento de pressão positiva ao final da expiração sobre a microcirculação sublingual em pacientes com síndrome do desconforto respiratório agudo.

OBJECTIVE: The aim of this study was to evaluate the impact of increased positive end-expiratory pressure on the sublingual microcirculation. METHODS: Adult patients who were sedated, under mechanical ventilation, and had a diagnosis of circulatory shock and acute respiratory distress syndrome were included. The positive end-expiratory pressure level was settled to obtain a plateau pressure of 30cmH2O and then maintained at this level for 20minutes. Microcirculatory (obtained by videomicroscopy) and hemodynamic variables were collected at baseline and compared with those at the end of 20min. RESULTS: Twelve patients were enrolled. Overall, the microcirculation parameters did not significantly change after increasing the positive end-expiratory pressure. However, there was considerable interindividual variability. There was a negative, moderate correlation between the changes in the De Backer score (r=-0.58, p=0.048), total vessel density (r=-0.60, p=0.039) and baseline values. The changes in total vessel density (r=0.54, p=0.07) and perfused vessel density (r=0.52, p=0.08) trended toward correlating with the changes in the mean arterial pressure. CONCLUSION: Overall, the microcirculation parameters did not significantly change after increasing the positive end-expiratory pressure. However, at individual level, such response was heterogeneous. The changes in the microcirculation parameters could be correlated with the baseline values and changes in the mean arterial pressure.

Microcirculation improvement after short-term infusion of vasopressin in septic shock is dependent on noradrenaline.

OBJECTIVES: To assess the impact of vasopressin on the microcirculation and to develop a predictive model to estimate the probability of microcirculatory recruitment in patients with septic shock. METHODS: This prospective interventional study included patients with septic shock receiving noradrenaline for less than 48 hours. We infused vasopressin at 0.04 U/min for one hour. Hemodynamic measurements, including sidestream dark-field imaging, were obtained immediately before vasopressin infusion, 1 hour after vasopressin infusion and 1 hour after vasopressin withdrawal. We defined patients with more than a 10% increase in total vascular density and perfused vascular density as responders. ClinicalTrials.gov: NCT02053675. RESULTS: Eighteen patients were included, and nine (50%) showed improved microcirculation after infusion of vasopressin. The noradrenaline dose was significantly reduced after vasopressin (p=0.001) and was higher both at baseline and during vasopressin infusion in the responders than in the non-responders. The strongest predictor for a favorable microcirculatory response was the dose of noradrenaline at baseline (OR=4.5; 95% CI: 1.2-17.0; p=0.027). For patients using a noradrenaline dose higher than 0.38 mcg/kg/min, the probability that microcirculatory perfusion would be improved with vasopressin was 53% (sensitivity 78%, specificity 77%). CONCLUSIONS: In patients with septic shock for no longer than 48 h, administration of vasopressin is likely to result in an improvement in microcirculation when the baseline noradrenaline dose is higher than 0.38 mcg/kg/min.

Factors associated with hospital mortality in renal transplant patients admitted to the intensive care unit with acute respiratory failure.

INTRODUCTION: The lungs are often involved in a variety of complications after kidney transplantation. Acute respiratory failure (ARF) is one of the most serious manifestations of pulmonary involvement. OBJECTIVE: To describe the main causes of ARF in kidney transplant patients who require intensive care and identify the factors associated with mortality. METHODS: This retrospective study evaluated adult patients with ARF admitted to the intensive care unit of a center with high volume of transplants from August 2013 to August 2015. Demographic, clinical, and transplant characteristics were analyzed. Multivariate logistic regression analysis was performed to identify factors associated with hospital mortality. RESULTS: 183 patients were included with age of 55.32 ± 13.56 years. 126 (68.8%) were deceased-donor transplant, and 37 (20.2%) patients had previous history of rejection. The ICU admission SAPS3 and SOFA score were 54.39 ± 10.32 and 4.81 ± 2.32, respectively. The main cause of hospitalization was community-acquired pneumonia (18.6%), followed by acute pulmonary edema (15.3%). Opportunistic infections were common: PCP (9.3%), tuberculosis (2.7%), and cytomegalovirus (2.2%). Factors associated with mortality were requirement for vasopressor (OD 8.13, CI 2.83 to 23.35, p < 0.001), invasive mechanical ventilation (OD 3.87, CI: 1.29 to 11.66, p = 0.016), and SAPS3 (OD 1.04, CI 1.0 to 1.08, p = 0.045). CONCLUSION: Bacterial pneumonia is the leading cause of ARF requiring intensive care, followed by acute pulmonary edema. Requirement for vasopressor, invasive mechanical ventilation and SAP3 were associated with hospital mortality.

Prevalence of cytomegalovirus disease in kidney transplant patients in an intensive care unit. / Prevalência de doença por citomegalovírus em transplantados renais em unidade de terapia intensiva.

OBJECTIVES: To define the frequency of cytomegalovirus disease among kidney transplant patients in an intensive care unit in which this complication was suspected and to identify predisposing factors and their possible impact on clinical outcome. METHODS: Retrospective observational study in which kidney transplant patients over the age of 18 years were hospitalized for any reason in an intensive care unit with at least one collection of samples to test for the presence of antigenemia or cytomegalovirus via polymerase chain reaction during hospitalization. Cytomegalovirus disease was defined as positive antigenemia or polymerase chain reaction above 500 copies/mL in the presence of symptoms and in the appropriate clinical setting, as judged by the attending physician. RESULTS: A total of 99 patients were included (age: 53.4 ± 12.8 years, 71.6% male). Cytomegalovirus disease was diagnosed in 39 patients (39.4%). Respiratory symptoms (51%), non-specific clinical worsening (20%) or gastrointestinal symptoms (14%) were the main reasons for exam collection. Transplant time was lower in those with cytomegalovirus disease than in those without this diagnosis (6.5 months and 31.2 months, p = 0.001), along with pulse therapy in the last 6 months (41% and 16.9%, p = 0.008) and previous use of thymoglobulin in the last year (35.9% and 6.8%, p < 0.001). In the logistic regression model, only the transplant time and the use of thymoglobulin were associated with a higher frequency of cytomegalovirus. There was no difference in clinical evolution between patients with and without cytomegalovirus disease. CONCLUSION: In kidney transplant patients suspected of cytomegalovirus disease, the prevalence was high. Transplant time less than 6 months, and the use of thymoglobulin in the last year should increase the intensivist's suspicion for this complication.

OBJETIVOS: Definir frequência de doença por citomegalovírus dentre pacientes transplantados renais na unidade de terapia intensiva nos quais houve a suspeita desta complicação; identificar fatores predisponentes e possível impacto na evolução clínica. MÉTODOS: Estudo retrospectivo observacional, no qual foram incluídos pacientes transplantados renais acima de 18 anos, internados por quaisquer motivos em uma unidade de terapia intensiva, com pelo menos uma coleta de antigenemia ou reação em cadeia da polimerase para citomegalovírus durante internação. Doença por citomegalovírus foi definida por antigenemia positiva ou reação em cadeia da polimerase acima de 500 cópias/mL, na presença de sintomas, no contexto clínico apropriado, conforme julgamento do médico assistente. RESULTADOS: Foram incluídos 99 pacientes (idade: 53,4 ± 12,8 anos, 71,6% homens). A doença por citomegalovírus foi diagnosticada em 39 pacientes (39,4%). Sintomas respiratórios (51%), piora clínica inespecífica (20%) ou sintomas gastrintestinais (14%) foram os principais motivos para coleta de exames. O tempo de transplante foi menor naqueles com doença por citomegalovírus em relação àqueles sem este diagnóstico (6,5 meses e 31,2 meses; p = 0,001), bem como uso de pulsoterapia nos últimos 6 meses (41% e 16,9%; p = 0,008) e uso prévio de timoglobulina no último ano (35,9% e 6,8%; p < 0,001). No modelo de regressão logística, somente o tempo de transplante e o uso de timoglobulina associaram-se à maior frequência de citomegalovírus. Não houve diferença na evolução clínica entre pacientes com ou sem doença por citomegalovírus. CONCLUSÃO: Em pacientes transplantados renais com suspeita de doença por citomegalovírus, a prevalência foi alta. O tempo de transplante menor que 6 meses e o uso de timoglobulina no último ano devem aumentar a suspeita do intensivista para esta complicação.

The diagnostic yield and complications of open lung biopsies in kidney transplant patients with pulmonary disease.

BACKGROUND: The purpose of this study was to assess the efficacy of open lung biopsy (OLB) in determining the specific diagnosis and the related complications in patients with undiagnosed diffuse pulmonary infiltrates. METHODS: This single center, retrospective study included adult kidney transplant patients who underwent OLB. The patients had diffuse pulmonary infiltrates without definitive diagnoses and failed to respond to empiric antibiotic treatment. We analyzed the number of specific diagnoses, changes in treatment and the occurrence of complications in these patients. A logistic regression was used to determine which variables were predictors of hospital mortality. RESULTS: From April 2010 to April 2014, 87 patients consecutively underwent OLB. A specific diagnosis was reached in 74 (85.1%) patients. In 46 patients (53%), their therapeutic management was changed after the OLB results. Twenty-five (28.7%) patients had complications related to the OLB. The hospital mortality rate was 25.2%. Age, SAPS3 score and complications related to the procedure were independent predictors of all-cause mortality. CONCLUSIONS: OLB is a high-risk procedure with a high diagnostic yield in kidney transplant patients with diffuse pulmonary infiltrates who did not have a definitive diagnosis and who failed to respond to empiric antibiotic treatment. Complications related to OLB were common and were independently associated with intra-hospital mortality.

Efeitos da solução balanceada em desfechos de curto prazo em pacientes com traumatismo craniencefálico: uma análise secundária do ensaio clínico randomizado BaSICS / Effects of balanced solution on short-term outcomes in traumatic brain injury patients: a secondary analysis of the BaSICS randomized trial

RESUMO Objetivo: Descrever os efeitos do uso de soluções balanceadas nos desfechos de curto prazo de pacientes com traumatismo craniencefálico incluídos no estudo BaSICS. Métodos: Os pacientes foram randomizados para receber solução salina 0,9% ou solução balanceada durante a internação em unidade de terapia intensiva. O desfecho primário foi mortalidade em 90 dias, já os desfechos secundários foram dias de vida e sem internação em unidade de terapia intensiva aos 28 dias. O desfecho primário foi avaliado por regressão logística bayesiana. O desfecho secundário foi avaliado usando regressão beta-binomial inflada de zeros bayesiana. Resultados: Incluímos 483 pacientes (236 no braço de solução salina 0,9% e 247 no braço de solução balanceada). Foram incluídos 338 pacientes (70%) com pontuação na escala de coma de Glasgow ≤ 12. A probabilidade geral de que soluções balanceadas estivessem associadas a maior mortalidade em 90 dias foi de 0,98 (RC de 1,48; ICr95% 1,04 - 2,09). Esse aumento de mortalidade foi particularmente perceptível em pacientes com pontuação na escala de coma de Glasgow abaixo de 6 no momento da inclusão (probabilidade de dano de 0,99). Soluções balanceadas foram associadas a -1,64 dia de vida e sem internação em unidade de terapia intensiva aos 28 dias (ICr95% -3,32 - 0,00) com probabilidade de dano de 0,97. Conclusão: Houve alta probabilidade de que soluções balanceadas estivessem associadas a alta mortalidade em 90 dias, menos dias de vida e sem internação em unidade de terapia intensiva aos 28 dias. ClinicalTrials.gov:NCT02875873

ABSTRACT Objective: To describe the effects of balanced solution use on the short-term outcomes of patients with traumatic brain injury enrolled in BaSICS trial. Methods: Patients were randomized to receive either 0.9% saline or balanced solution during their intensive care unit stay. The primary endpoint was 90-day mortality, and the secondary outcomes were days alive and free of intensive care unit stay at 28 days. The primary endpoint was assessed using Bayesian logistic regression. The secondary endpoint was assessed using a Bayesian zero-inflated beta binomial regression. Results: We included 483 patients (236 in the 0.9% saline arm and 247 in the balanced solution arm). A total of 338 patients (70%) with a Glasgow coma scale score ≤ 12 were enrolled. The overall probability that balanced solutions were associated with higher 90-day mortality was 0.98 (OR 1.48; 95%CrI 1.04 - 2.09); this mortality increment was particularly noticeable in patients with a Glasgow coma scale score below 6 at enrollment (probability of harm of 0.99). Balanced solutions were associated with -1.64 days alive and free of intensive care unit at 28 days (95%CrI -3.32 - 0.00) with a probability of harm of 0.97. Conclusion: There was a high probability that balanced solutions were associated with high 90-day mortality and fewer days alive and free of intensive care units at 28 days. ClinicalTrials.gov:NCT02875873