Vitamin D Status and Potential Therapeutic Options in Critically Ill Patients: A Narrative Review of the Clinical Evidence

Vitamin D covers roles of paramount importance in the regulation of multiple physiological pathways of the organism. The metabolism of vitamin D involves kidney–liver crosstalk and requires an adequate function of these organs, where vitamin D is progressively turned into active forms. Vitamin D deficiency has been widely reported in patients living in the community, being prevalent among the most vulnerable subjects. It has been also documented in many critically ill patients upon admission to the intensive care unit. In this context, vitamin D deficiency may represent a risk factor for the development of life-threatening clinical conditions (e.g., infection and sepsis) and worse clinical outcomes. Several researchers have investigated the impact of vitamin D supplementation showing its feasibility, safety, and effectiveness, although conflicting results have put into question its real benefit in critically ill patients. The existing studies included heterogeneous critically ill populations and used slightly different protocols of vitamin D supplementation. For these reasons, pooling up the results is difficult and not conclusive. In this narrative review, we described vitamin D physiology and the pathophysiology of vitamin D depletion with a specific focus on critically ill patients with liver dysfunction, acute kidney injury, acute respiratory failure, and sepsis

Vitamin D Status and Potential Therapeutic Options in Critically Ill Patients: A Narrative Review of the Clinical Evidence

Vitamin D covers roles of paramount importance in the regulation of multiple physiological pathways of the organism. The metabolism of vitamin D involves kidney–liver crosstalk and requires an adequate function of these organs, where vitamin D is progressively turned into active forms. Vitamin D deficiency has been widely reported in patients living in the community, being prevalent among the most vulnerable subjects. It has been also documented in many critically ill patients upon admission to the intensive care unit. In this context, vitamin D deficiency may represent a risk factor for the development of life-threatening clinical conditions (e.g., infection and sepsis) and worse clinical outcomes. Several researchers have investigated the impact of vitamin D supplementation showing its feasibility, safety, and effectiveness, although conflicting results have put into question its real benefit in critically ill patients. The existing studies included heterogeneous critically ill populations and used slightly different protocols of vitamin D supplementation. For these reasons, pooling up the results is difficult and not conclusive. In this narrative review, we described vitamin D physiology and the pathophysiology of vitamin D depletion with a specific focus on critically ill patients with liver dysfunction, acute kidney injury, acute respiratory failure, and sepsis

Sepsis uncouples serum C-peptide and insulin levels in critically ill patients with type 2 diabetes mellitus.

OBJECTIVE To assess the effects of sepsis and exogenous insulin on C-peptide levels and C-peptide to insulin ratios in intensive care unit (ICU) patients with type 2 diabetes mellitus (T2DM). DESIGN, SETTING AND PARTICIPANTS In this prospective, observational, single-centre study, we enrolled 31 ICU-admitted adults with T2DM. We measured serum C-peptide and insulin levels during the first 3 days of ICU stay and recorded characteristics of exogenous insulin therapy. Patients were compared on the basis of the presence of sepsis, and their exposure to exogenous insulin therapy. C-peptide levels were also measured in eight healthy subjects. MAIN OUTCOME MEASURES Serum insulin and C-peptide levels during the first 3 days in ICU. RESULTS Median C-peptide levels were higher in the ICU population compared with healthy subjects (10.9 [IQR, 8.2 -14.1] 4.8 [IQR, 4.6-5.1] nmol/L, < 0.01). Sepsis was present in 25 ICU patients (81%). Among ICU patients unexposed to exogenous insulin, the 11 patients with sepsis had higher median C-peptide levels compared with the six non-septic patients (2.5 [IQR, 1.8-3.7] 1.7 [IQR, 0.8-2.2] nmol/L, = 0.04), and a threefold higher C-peptide to insulin ratio (45 [IQR, 37-62] 13 [IQR, 11-17], = 0.03). However, septic patients exposed to exogenous insulin had lower median C-peptide levels (1.2 [IQR, 0.7-2.3] nmol/L, = 0.01) and C-peptide to insulin ratios (5 [IQR, 2-10], < 0.01) compared with insulin-free septic patients. The C-peptide to insulin ratio was significantly associated with white cell count and severity of illness in insulin-free septic patients. CONCLUSION C-peptide levels were elevated in critically ill patients with T2DM. In this population, sepsis increased C-peptide levels and uncoupled serum C-peptide and insulin levels. Exogenous insulin decreased both C-peptide levels and C-peptide to insulin ratios

The hemodynamic effects of warm versus room-temperature crystalloid fluid bolus therapy in post-cardiac surgery patients.

INTRODUCTION The contribution of fluid temperature to the effect of crystalloid fluid bolus therapy (FBT) in post-cardiac surgery patients is unknown. We evaluated the hemodynamic effects of FBT with fluid warmed to 40°C (warm FBT) versus room-temperature fluid. METHODS In this single centre prospective before-and-after study, we evaluated the effects of 500 ml of warm versus room-temperature compound sodium lactate administered over 15% of baseline immediately after FBT and effect dissipation if the CI returned to 10% increase and dissipation as return to <3 mmHg of baseline. RESULTS Hypotension (56%) and low CI (40%) typically triggered FBT. Temperature decreased >0.3°C in 13 (52%) patients after room-temperature FBT versus 0 (0%) after warm FBT (p < 0.01). CI and MAP responsiveness was similar (16 [64%] versus 11 [44%], p = 0.15 and 15 [60%] versus 17 [68%], p = 0.77, respectively). Among CI responders, CI increased more with room-temperature FBT (+0.6 [IQR, 0.5-1.1] versus +0.5 [IQR, 0.4-0.6] L/min/m2, p = 0.01). However, dissipation was more common after room-temperature versus warm FBT (9/16 [56%] versus 1/11 [9%], p = 0.02). CONCLUSION In postoperative cardiac surgery patients, warm FBT preserved core temperature and induced smaller but more sustained CI increases among responders. Fluid temperature appears to impact both core temperature and the duration of CI response

Physiological effects of awake prone position in acute hypoxemic respiratory failure

Abstract Background The effects of awake prone position on the breathing pattern of hypoxemic patients need to be better understood. We conducted a crossover trial to assess the physiological effects of awake prone position in patients with acute hypoxemic respiratory failure. Methods Fifteen patients with acute hypoxemic respiratory failure and PaO2/FiO2  0.99) and ΔP L (9 [7–11] cmH2O vs. 8 [5–9], p = 0.17). Airway resistance and time constant were higher in prone vs. supine position (9 cmH2O s arbitrary units−3 [4–11] vs. 6 [4–9], p = 0.05; 0.53 s [0.32–61] vs. 0.40 [0.37–0.44], p = 0.03). Prone position increased EELI (3887 arbitrary units [3414–8547] vs. 1456 [959–2420], p = 0.002) and promoted V T distribution towards dorsal lung regions without affecting V T size and lung compliance: this generated lower dynamic strain (0.21 [0.16–0.24] vs. 0.38 [0.30–0.49], p = 0.004). The magnitude of pendelluft phenomenon was not different between study phases (55% [7–57] of V T in prone vs. 31% [14–55] in supine position, p > 0.99). Conclusions Prone position improves oxygenation, increases EELI and promotes V T distribution towards dependent lung regions without affecting V T size, ΔP L, lung compliance and pendelluft magnitude. Prone position reduces respiratory rate and increases ΔP ES because of positional increases in airway resistance and prolonged expiratory time. Because high ΔP ES is the main mechanistic determinant of self-inflicted lung injury, caution may be needed in using awake prone position in patients exhibiting intense ΔP ES. Clinical trail registeration: The study was registered on clinicaltrials.gov (NCT03095300) on March 29, 2017

Respiratory physiology of COVID-19-induced respiratory failure compared to ARDS of other etiologies

Abstract Background Whether respiratory physiology of COVID-19-induced respiratory failure is different from acute respiratory distress syndrome (ARDS) of other etiologies is unclear. We conducted a single-center study to describe respiratory mechanics and response to positive end-expiratory pressure (PEEP) in COVID-19 ARDS and to compare COVID-19 patients to matched-control subjects with ARDS from other causes. Methods Thirty consecutive COVID-19 patients admitted to an intensive care unit in Rome, Italy, and fulfilling moderate-to-severe ARDS criteria were enrolled within 24 h from endotracheal intubation. Gas exchange, respiratory mechanics, and ventilatory ratio were measured at PEEP of 15 and 5 cmH2O. A single-breath derecruitment maneuver was performed to assess recruitability. After 1:1 matching based on PaO2/FiO2, FiO2, PEEP, and tidal volume, COVID-19 patients were compared to subjects affected by ARDS of other etiologies who underwent the same procedures in a previous study. Results Thirty COVID-19 patients were successfully matched with 30 ARDS from other etiologies. At low PEEP, median [25th–75th percentiles] PaO2/FiO2 in the two groups was 119 mmHg [101–142] and 116 mmHg [87–154]. Average compliance (41 ml/cmH2O [32–52] vs. 36 ml/cmH2O [27–42], p = 0.045) and ventilatory ratio (2.1 [1.7–2.3] vs. 1.6 [1.4–2.1], p = 0.032) were slightly higher in COVID-19 patients. Inter-individual variability (ratio of standard deviation to mean) of compliance was 36% in COVID-19 patients and 31% in other ARDS. In COVID-19 patients, PaO2/FiO2 was linearly correlated with respiratory system compliance (r = 0.52 p = 0.003). High PEEP improved PaO2/FiO2 in both cohorts, but more remarkably in COVID-19 patients (p = 0.005). Recruitability was not different between cohorts (p = 0.39) and was highly inter-individually variable (72% in COVID-19 patients and 64% in ARDS from other causes). In COVID-19 patients, recruitability was independent from oxygenation and respiratory mechanics changes due to PEEP. Conclusions Early after establishment of mechanical ventilation, COVID-19 patients follow ARDS physiology, with compliance reduction related to the degree of hypoxemia, and inter-individually variable respiratory mechanics and recruitability. Physiological differences between ARDS from COVID-19 and other causes appear small