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.

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.

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.

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.

Is venous blood drawn from femoral access adequate to estimate the central venous oxygen saturation and arterial lactate levels in critically ill patients?

OBJECTIVES: The purpose of this study was to test if venous blood drawn from femoral access can be used to estimate the central venous oxygen saturation and arterial lactate levels in critically ill patients. METHODS: Bland-Altman analysis and Spearman correlations were used to compare the femoral venous oxygen saturation and central venous oxygen saturation as well as arterial lactate levels and femoral lactate. A pre-specified subgroup analysis was conducted in patients with signs of hypoperfusion. In addition, the clinical agreement was also investigated. RESULTS: Blood samples were obtained in 26 patients. In 107 paired samples, there was a moderate correlation (r = 0.686, p < 0.0001) between the central venous oxygen saturation and femoral venous oxygen saturation with a bias of 8.24 ± 10.44 (95% limits of agreement: -12.23 to 28.70). In 102 paired samples, there was a strong correlation between the arterial lactate levels and femoral lactate levels (r = 0.972, p < 0.001) with a bias of -2.71 ± 9.86 (95% limits of agreement: -22.03 to 16.61). The presence of hypoperfusion did not significantly change these results. The clinical agreement for venous saturation was inadequate, with different therapeutic decisions in 22.4% of the situation; for lactate, this was the case only in 5.2% of the situations. CONCLUSION: Femoral venous oxygen saturation should not be used as a surrogate of central venous oxygen saturation. However, femoral lactate levels can be used in clinical practice, albeit with caution.