A Secondary Retrospective Analysis of the Predictive Value of Neutrophil-Reactive Intensity (NEUT-RI) in Septic and Non-Septic Patients in Intensive Care.

BACKGROUND: Effective identification and management in the early stages of sepsis are critical for achieving positive outcomes. In this context, neutrophil-reactive intensity (NEUT-RI) emerges as a promising and easily interpretable parameter. This study aimed to assess the predictive value of NEUT-RI in diagnosing sepsis and to evaluate its prognostic significance in distinguishing 28-day mortality outcomes. MATERIALS: This study is a secondary, retrospective, observational analysis. Clinical data upon ICU admission were collected. We enrolled septic patients and a control group of critically ill patients without sepsis criteria. The patients were divided into subgroups based on renal function for biomarker evaluation with 28-day outcomes reported for septic and non-septic patients. RESULTS: A total of 200 patients were included in this study. A significant difference between the "septic" and "non-septic" groups was detected in the NEUT-RI plasma concentration (53.80 [49.65-59.05] vs. 48.00 [46.00-49.90] FI, p < 0.001, respectively). NEUT-RI and procalcitonin (PCT) distinguished between not complicated sepsis and septic shock (PCT 1.71 [0.42-12.09] vs. 32.59 [8.83-100.00], <0.001 and NEUT-RI 51.50 [47.80-56.30] vs. 56.20 [52.30-61.92], p = 0.005). NEUT-RI, PCT, and CRP values were significantly different in patients with "renal failure". NEUT-RI and PCT at admission in the ICU in the septic group were higher in patients who died (58.80 [53.85-73.10] vs. 53.05 [48.90-57.22], p = 0.005 and 39.56 [17.39-83.72] vs. 3.22 [0.59-32.32], p = 0.002, respectively). Both NEUT-RI and PCT showed a high negative predictive value and low positive predictive value. CONCLUSIONS: The inflammatory biomarkers assessed in this study offer valuable support in the early diagnosis of sepsis and could have a possible role in anticipating the outcome. NEUT-RI elevation appears particularly promising for early sepsis detection and severity discrimination upon admission.

Foot drop in critically ill patients: a narrative review of an elusive complication with intricate implications for recovery and rehabilitation.

Foot drop is a condition characterized by the inability to lift the foot upwards towards the shin bone. This condition may affect a proportion of critically ill patients, impacting on their recovery after the acute phase of the illness. The occurrence of foot drop in critical care patients may result from various underlying causes, including neurological injuries, muscular dysfunction, nerve compression, or vascular compromise. Understanding the etiology and assessing the severity of foot drop in these patients is essential for implementing appropriate management strategies and ensuring better patient outcomes. In this comprehensive review, we explore the complexities of foot drop in critically ill patients. We search for the potential risk factors that contribute to its development during critical illness, the impact it has on patients' functional abilities, and the various diagnostic techniques adopted to evaluate its severity. Additionally, we discuss current treatment approaches, rehabilitation strategies, and preventive measures to mitigate the adverse effects of foot drop in the critical care setting. Furthermore, we explore the roles of critical care physical therapists, neurologists, and other healthcare professionals in the comprehensive care of patients with foot drop syndrome and in such highlighting the importance of a multidisciplinary approach.

The Potential Role of Neutrophil-Reactive Intensity (NEUT-RI) in the Diagnosis of Sepsis in Critically Ill Patients: A Retrospective Cohort Study.

The diagnosis of sepsis is often difficult and belated, substantially increasing mortality in affected patients. Its early identification allows for us to choose the most appropriate therapies in the shortest time, improving patients' outcomes and eventually their survival. Since neutrophil activation is an indicator of an early innate immune response, the aim of the study was to evaluate the role of Neutrophil-Reactive Intensity (NEUT-RI), which is an indicator of their metabolic activity, in the diagnosis of sepsis. Data from 96 patients consecutively admitted to the Intensive Care Unit (ICU) were retrospectively analyzed (46 patients with and 50 without sepsis). Patients with sepsis were further divided between sepsis and septic shock according to the severity of the illness. Patients were subsequently classified according to renal function. For the diagnosis of sepsis, NEUT-RI showed an AUC of >0.80 and a better negative predictive value than Procalcitonin (PCT) and C-reactive protein (CRP) (87.4% vs. 83.9% and 86.6%, p = 0.038). Unlike PCT and CRP, NEUT-RI did not show a significant difference within the "septic" group between patients with normal renal function and those with renal failure (p = 0.739). Similar results were observed among the "non-septic" group (p = 0.182). The increase in NEUT-RI values could be useful in the early ruling-out of sepsis, and it does not appear to be influenced by renal failure. However, NEUT-RI has not proved to be efficient in discriminating the severity of sepsis at the time of admission. Larger, prospective studies are needed to confirm these results.

Electrolytes, albumin and acid base equilibrium during laparoscopic surgery.

BACKGROUND: Surgery, causing inflammation, disrupts endothelial permeability leading to movement of fluids and albumin across the vascular barrier. Fluid therapy for restoring circulatory homeostasis may lead to positive fluid balance which has been shown to increase morbidity and mortality in surgical patients. The current investigation aims to describe physio-pathological changes in circulating albumin, fluid and electrolyte balance, and acid-base equilibrium in a cohort of patients undergoing laparoscopic surgery under general anesthesia. METHODS: Single-center prospective observational study. Patients undergoing laparoscopic colorectal surgery were screened for eligibility. Before surgery, the baseline fasting conditions were homogenized. Hemoglobin, urinary and plasmatic were collected before surgery and then at pre-defined timepoints. Albumin/creatinine ratio was measured before and after surgery. Expected and actual circulating Sodium concentrations were compared according to a physiological theoretical model. Assessment and quantification of changes in major electrolytes, albumin and acid-base balance was defined as the primary outcome of the study. RESULTS: Thirty-eight patients were enrolled in the protocol. Patients had a positive electrolytes (Na+ 295 [244-375] mmol, Cl- 234 [195-295] mmol, K+ 16.8 [12.0-21.4] mmol) and fluid balance (2165 [1727-2728] mL). The positive fluid balance was associated with stable chloride (105 [103-107], end study vs. 103 [102-106] mmol/L, baseline, P not significant) and potassium (4.2 [3.8-4.4], end study vs. 4.1 [3.6-4.4] mmol/L, baseline, P not significant) levels, but sodium concentrations decreased over time (138 [137-140], end study vs. 139 [138-141] mmol/L, baseline, P<0.05). The albumin/creatinine ratio was higher at the end of surgery 134 [61-267] vs. 7 [4-14], P<0.001). CONCLUSIONS: Data from patients undergoing colorectal laparoscopic surgery showed a positive fluid balance, decreased circulating albumin and increased albuminuria. A positive sodium balance was not always associated with an increase in sodium plasma concentration.

The furosemide stress test, electrolyte response and Renal Index in critically ill patients.

BACKGROUND: Acute kidney injury (AKI) is a common syndrome in critically ill patients. The diagnostic ability of traditional markers such as serum creatinine has recently been questioned, and the use of newer tests such as the furosemide stress test or the ultrasound assessment of renal resistive index have been proposed. Aim of the present study was to compare the response to a furosemide stress test, the Renal Index in mechanically ventilated patients with and without acute kidney injury at admission, and who did or did not develop AKI at day three, among those with normal renal function at the CIU admission. METHODS: Prospective observational study in consecutive mechanically ventilated patients admitted in a general intensive care. Furosemide stress test and ultrasonographical Renal Index were performed at the admission and clinical and laboratory data were collected before and two hours after the furosemide stress text. The urine output after the first and the second hours was recorded. RESULTS: Forty patients were enrolled, 19 of whom had AKI at admission. The Renal Index was significantly higher in patients with AKI (0.77±0.07 vs. 0.72±0.08, P=0.027); patients with AKI had a significantly lower urine output after the furosemide stress test (400 [340; 1400] vs.1525 [400; 2550] mL; P=0.013). The plasma concentrations of sodium, potassium and chloride were not different before and after the furosemide stress test in patients with and without AKI, whereas in patients with AKI, the total urine output of sodium, potassium and chloride were significantly lower compared to patients without AKI. Similar results were found in patients without AKI at admission and who developed AKI at day three as compared to those who did not develop AKI. CONCLUSIONS: The response to the furosemide stress test and the Renal Index could be used as additional tools to evaluate the kidney function in critically ill patients.

Hyperoxia and oxidative stress in anesthesia and critical care medicine.

Oxygen administration is particularly relevant in patients undergoing surgery under general anesthesia and in those who suffer from acute or critical illness. Nevertheless, excess O2, or hyperoxia, is also known to be harmful. Toxicity arises from the enhanced formation of reactive oxygen species (ROS) that, exceeding the antioxidant defense, may generate oxidative stress. Oxidative stress markers are used to quantify ROS toxicity in clinical and non-clinical settings and represent a promising tool to assess the optimal FiO2 in anesthesia and critical care setting. Despite controversial, the guidelines for the regulation of FiO2 in such settings suggest the adoption of high perioperative oxygen levels. However, hyperoxia has also been shown to be an independent mortality risk factor in critically ill patients. In this literature review, we discuss the biochemical mechanisms behind oxidative stress and the available biomarkers for assessing the pro-oxidant vs antioxidant status. Then, we summarize recent knowledge on the hyperoxia-related consequences in the most common anesthesia and critical care settings, such as traumatic brain injury or cardiac arrest. To this purpose, we searched the PubMed database according to the following combination of key words: ("hyperoxia" OR "FiO2" OR "oxygen therapy") AND ("oxidative stress" OR "ROS" OR "RNS" OR "lipid peroxidation") AND ("anesthesia" OR "surgery" OR "intensive care"). We focused in the results from the past 20 years. Available evidence points toward a conservative monitoring and use of oxygen, unless there is solid proof of its efficacy.

Oxidative Stress Markers to Investigate the Effects of Hyperoxia in Anesthesia.

Oxygen (O2) is commonly used in clinical practice to prevent or treat hypoxia, but if used in excess (hyperoxia), it may act as toxic. O2 toxicity arises from the enhanced formation of Reactive Oxygen Species (ROS) that exceed the antioxidant defenses and generate oxidative stress. In this study, we aimed at assessing whether an elevated fraction of inspired oxygen (FiO2) during and after general anesthesia may contribute to the unbalancing of the pro-oxidant/antioxidant equilibrium. We measured five oxidative stress biomarkers in blood samples from patients undergoing elective abdominal surgery, randomly assigned to FiO2 = 0.40 vs. 0.80: hydroperoxides, antioxidants, nitrates and nitrites (NOx), malondialdehyde (MDA), and glutathionyl hemoglobin (HbSSG). The MDA concentration was significantly higher 24 h after surgery, and the body antioxidant defense lower, in the FiO2 = 0.80 group with respect to both the FiO2 = 0.40 group and the baseline values (p ≤ 0.05, Student's t-test). HbSSG in red blood cells was also higher in the FiO2 = 0.80 group at the end of the surgery. NOx was higher in the FiO2 = 0.80 group than the FiO2 = 0.40 group at t = 2 h after surgery. MDA, the main end product of the peroxidation of polyunsaturated fatty acids directly influenced by FiO2, may represent the best marker to assess the pro-oxidant/antioxidant equilibrium after surgery.

Conscious sedation in critically ill patients is associated with stressors perception lower than assessed by caregivers.

BACKGROUND: In ICU, the stay is frequently a stressful experience. Caregivers may help to understand patients' perceptions; however, their reliability is uncertain. Despite the recent recommendations of lighter sedation targets, little is known about the impact of "conscious sedation" on ICU patients memories. Purpose of this prospective, observational study is to analyze the stress perception in consciously-sedated ICU-patients, comparing it to caregivers and staff members. METHODS: Twenty-nine high-risk ICU-patients treated with awake/cooperative sedation were enrolled. Before discharge, patients received a validated questionnaire for ICU stressors evaluation, also administered to their main caregiver (N.=29), to caregivers of other ICU patients not enrolled in the study (N.=33) and to staff members (ICU nurses, attending physicians, residents, medical students, N.=56). RESULTS: Total stress score was: patients 141±41, patient relatives 210±63, other relatives: 202±73, ICU staff: 232±44, P<0.001. Among patients, older age (P=0.031), longer ICU-stay (P=0.018) and awake-sedation (P=0.022) were associated with lower stress; sex and illness severity had no effect; mechanical ventilation length (P=0.021) and agitation (P=0.029) were associated with higher stress. Nurses tended to overestimate stressors more than attending physicians and trainees. Within staff members, age (P=0.021) and years of experience (P=0.069) were positively associated with overestimation. CONCLUSIONS: Conscious sedation is associated with stress perception lower than stress assessed by caregivers: relatives and staff members tend to overestimate ICU patient stress, more so with increasing age or expertise. A number of stressors underestimated by staff and families could be target of specific interventions to ameliorate quality of life during ICU stay.

Ammonium tetrathiomolybdate following ischemia/reperfusion injury: Chemistry, pharmacology, and impact of a new class of sulfide donor in preclinical injury models.

BACKGROUND: Early revascularization of ischemic organs is key to improving outcomes, yet consequent reperfusion injury may be harmful. Reperfusion injury is largely attributed to excess mitochondrial production of reactive oxygen species (ROS). Sulfide inhibits mitochondria and reduces ROS production. Ammonium tetrathiomolybdate (ATTM), a copper chelator, releases sulfide in a controlled and novel manner, and may offer potential therapeutic utility. METHODS AND FINDINGS: In vitro, ATTM releases sulfide in a time-, pH-, temperature-, and thiol-dependent manner. Controlled sulfide release from ATTM reduces metabolism (measured as oxygen consumption) both in vivo in awake rats and ex vivo in skeletal muscle tissue, with a superior safety profile compared to standard sulfide generators. Given intravenously at reperfusion/resuscitation to rats, ATTM significantly reduced infarct size following either myocardial or cerebral ischemia, and conferred survival benefit following severe hemorrhage. Mechanistic studies (in vitro anoxia/reoxygenation) demonstrated a mitochondrial site of action (decreased MitoSOX fluorescence), where the majority of damaging ROS is produced. CONCLUSIONS: The inorganic thiometallate ATTM represents a new class of sulfide-releasing drugs. Our findings provide impetus for further investigation of this compound as a novel adjunct therapy for reperfusion injury.

Melatonin Pharmacological Blood Levels Increase Total Antioxidant Capacity in Critically Ill Patients.

In this study, the aim was to test the biochemical effects of melatonin supplementation in Intensive Care Unit (ICU) patients, since their blood levels are decreased. Sixty-four patients were enrolled in the study. From the evening of the 3rd ICU day, patients were randomized to receive oral melatonin (3 mg, group M) or placebo (group P) twice daily, at 20:00 and 24:00, until discharged. Blood was taken (at 00:00 and 14:00), on the 3rd ICU day to assess basal nocturnal melatonin values, and then during the treatment period on the 4th and 8th ICU days. Melatonin, total antioxidant capacity, and oxidative stress were evaluated in serum. Melatonin circadian rhythm before treatment was similar in the two groups, with a partial preservation of the cycle. Four hours from the 1st administration (4th ICU day, 00:00), melatonin levels increased to 2514 (982.3; 7148) pg·mL-1 in group M vs. 20.3 (14.7; 62.3) pg·mL-1 in group P (p < 0.001). After five treatment days (8th ICU day), melatonin absorption showed a repetitive trend in group M, while in group P nocturnal secretion (00:00) was impaired: 20 (11.5; 34.5) pg·mL-1 vs. 33.8 (25.0; 62.2) on the 3rd day (p = 0.029). Immediately from the beginning of treatment, the total antioxidant capacity was significantly higher in melatonin treated subjects at 00:00; a significant correlation was found between total antioxidant capacity and blood melatonin values (ρ = 0.328; p < 0.001). The proposed enteral administration protocol was adequate, even in the early phase, to enhance melatonin blood levels and to protect the patients from oxidative stress. The antioxidant effect of melatonin could play a meaningful role in the care and well-being of these patients.

Neurological assessment with validated tools in general ICU: multicenter, randomized, before and after, pragmatic study to evaluate the effectiveness of an e-learning platform for continuous medical education.

BACKGROUND: International guidelines recommend systematic assessment of pain, agitation/sedation and delirium with validated scales for all ICU patients. However, these evaluations are often not done. We have created an e-learning training platform for the continuous medical education, and assessed its efficacy in increasing the use of validated tools by all medical and nursing staff of the participating ICUs during their daily practice. METHODS: Multicenter, randomized, before and after study. The eight participating centers were randomized in two groups, and received training at different times. The use of validated tools (Verbal Numeric Rating or Behavioral Pain Scale for pain; Richmond Agitation-Sedation Scale for agitation; Confusion Assessment Method for the ICU for delirium) was evaluated from clinical data recorded in medical charts during a week, with follow-up up to six months after the training. All the operators were invited to complete a questionnaire, at baseline and after the training. RESULTS: Among the 374 nurses and physicians involved, 140 (37.4%) completed at least one of the three courses. The assessment of pain (38.1 vs. 92.9%, P<0.01) and delirium (0 vs. 78.6%, P<0.01) using validated tools significantly increased after training. Observation in the follow-up showed further improvement in delirium monitoring, with no signs of extinction for pain and sedation/agitation measurements. CONCLUSIONS: This e-learning program shows encouraging effectiveness, and the increase in the use of validated tools for neurological monitoring in critically ill patients lasts over time.

Noninvasive CPAP with face mask: comparison among new air-entrainment masks and the Boussignac valve.

BACKGROUND: The performances of 2 noninvasive CPAP systems (high flow and low flow air-entrainment masks) were compared to the Boussignac valve in 3 different scenarios. METHODS: Scenario 1: pneumatic lung simulator with a tachypnea pattern (tidal volume 800 mL at 40 breaths/min). Scenario 2: Ten healthy subjects studied during tidal breaths and tachypnea. Scenario 3: Twenty ICU subjects enrolled for a noninvasive CPAP session. Differences between set and effective CPAP level and F(IO(2)), as well as the lowest airway pressure and the pressure swing around the imposed CPAP level, were analyzed. The lowest airway pressure and swing were correlated to the pressure-time product (area of the airway pressure curve below the CPAP level) measured with the simulator. P(aO(2)) was a subject's further performance index. RESULTS: Lung simulator: Boussignac F(IO(2)) was 0.54, even if supplied with pure oxygen. The air-entrainment masks had higher swing than the Boussignac (P = .007). Pressure-time product correlated better with pressure swing (Spearman correlation coefficient [ρ] = 0.97) than with lowest airway pressure (ρ = 0.92). In healthy subjects, the high-flow air-entrainment mask showed lower difference between set and effective F(IO(2)) (P < .001), and lowest airway pressure (P < .001), compared to the Boussignac valve. In all measurements the Boussignac valve showed higher than imposed CPAP level (P < .001). In ICU subjects the high-flow mask had lower swing than the Boussignac valve (P = .03) with similar P(aO(2)) increase. CONCLUSIONS: High-flow air-entrainment mask showed the best performance in human subjects. During high flow demand, the Boussignac valve delivered lower than expected F(IO(2)) and showed higher dynamic hyper-pressurization than the air-entrainment masks.

Pharmacokinetics of orally administered melatonin in critically ill patients.

Critically ill patients exhibit reduced melatonin secretion, both in nocturnal peaks and basal daytime levels. Oral melatonin supplementation may be useful for known sedative and antioxidant properties. Its early enteral absorption and daily pharmacokinetics were determined in two cohorts of six high-risk patients in this prospective trial. During their third and fourth Intensive Care Unit (ICU) day, they underwent two different sets of repeated blood samples to detect serum melatonin levels through radio-immuno-assay. Cohort 1: samples taken at 20:00, 20:45, 21:30, 24:00, 03:00, 06:00, 14:00, 20:00 to describe the daily pharmacokinetics. Cohort 2: 20:00, 20:05, 20:10, 20:20, 20:30, 20:45 to study the early absorption. On ICU day 3, endogenous levels were measured, while the absorption of exogenous melatonin was determined on ICU day 4 after administration, at 20:00, of 3 mg melatonin. All basal levels were below the expected values. Following enteral administration, pharmacological levels were already reached in 5 min, with a serum peak after 16 min (half-absorption time: 3 min 17 s). The maximum serum level observed was 11040 pg/mL and the disappearance rate indicated a half-elimination time of 1 hr 34 min. Serum melatonin levels decreased significantly after midnight; pharmacological levels were maintained up to 10 hr following administration. No excessive sleepiness was reported in this patient group. Critically ill patients exhibited reduced melatonin secretion, as reported in the literature. Despite the critical illness, the oral bioavailability was satisfactory: serum levels after oral administration showed basically unchanged intestinal absorption, while disappearance rate was slower than reported elsewhere in healthy volunteers.

Actigraphic monitoring in critically ill patients: preliminary results toward an "observation-guided sedation".

PURPOSE: The aim of this study is to evaluate continuous wrist actigraphy (measurement of limb movements) in intensive care unit patients as a neurologic status monitoring. MATERIALS AND METHODS: This is a prospective, observational study on motor activity of adult patients using wrist actigraphs. Nurses recorded the number of sleep and agitation hours as well as assessed pain and anxiety level (verbal numeric rating) and the agitation/sedation level (Richmond Agitation-Sedation Scale). RESULTS: Thirteen mechanically ventilated patients were studied during their whole intensive care unit stay (total, 165 patients/d). The number of surveyed movements was gathered for each hour, obtaining an estimation of patient motor status. This measure was different between days and nights (33.3 [20.3-49.0] vs 8.5 [4.4-13.8]; P < .001), with a correlation with sleeping hours estimated by nurses (P = .017 during the days [D], P < .001 during the nights [N]), agitation hours (P = .002 D, P = .017 N), Richmond Agitation-Sedation Scale value (P < .001 D and N), pain (P = .012 D), and anxiety (P < .001 D) verbal numeric rating. No differences were found using epochs of 15 or 120 seconds. Compliance with patients and nurses was acceptable. CONCLUSIONS: Patients' limb movements were significantly related to all studied neurologic status indexes. Continuous actigraphy measuring may become important as a clinical tool both to guide utilization of sedative drugs and to enhance early recognition and management of agitation.

Oxycodone controlled-release as first-choice therapy for moderate-to-severe cancer pain in Italian patients: results of an open-label, multicentre, observational study.

BACKGROUND AND OBJECTIVES: Cancer pain affects patients at all stages of the disease and there are clear guidelines for its management. Morphine is considered the first-choice strong opioid in the treatment of moderate-to-severe pain; however, numerous studies have shown that oxycodone controlled-release (CR) has a similar efficacy and safety profile. The purpose of this study was to evaluate the efficacy and tolerability of oxycodone CR as a first-line strong opioid for the treatment of moderate-to-severe pain in Italian cancer patients. METHODS: This was a prospective, open-label, multicentre, observational trial carried out at 15 locations across Italy. Patients with a referral for cancer-related pain of > or =5 on a 10-point numerical rating scale were enrolled. Patients were treated with oral oxycodone CR and monitored for 21 days. Dosage was individualized for each patient and up-titrated until effective pain control was achieved. Pain, adverse events and quality-of-life scores were assessed throughout the study. RESULTS: 390 patients (174 females and 216 males) with a mean age of 66 +/- 11 years were evaluated. The average daily dose ranged from 22.84 on day 1 to 40 mg/day on day 21. Pain intensity (assessed on a 10-point numerical rating scale) decreased significantly within 1 day of treatment commencement (p = 0.00001) and continued to decrease throughout the study period (from a mean 7.22 at baseline to a mean 2.11 points on day 21). Adverse events were mild to moderate in intensity and consisted of common opioid-related events. Ten patients (2.6%) discontinued the study because of adverse events and four (1%) because of uncontrolled pain. All aspects of activities of daily life assessed were improved by study end. CONCLUSIONS: Oxycodone CR is efficacious and well tolerated as a first-line strong opioid for the treatment of moderate-to-severe cancer-related pain in Italian patients.