Nociception level response to calibrated stimulations in children: First assessment of the nociception level index in pediatric anesthesia.

INTRODUCTION: Intraoperative monitoring of nociception has made great progress in adult anesthesia. However, pediatric data are scarce. The Nociception Level (NOL) is one of the most recent indexes of nociception. Its originality is that it provides a multiparametric assessment of nociception. In adults, NOL monitoring allowed lower perioperative opioid requirements, hemodynamic stability, and qualitative postoperative analgesia. So far, the NOL has never been used in children. Our objective was to validate the ability of NOL to provide a quantitative assessment of nociception in anesthetized children. METHODS: In 5-12 years old children anesthetized with sevoflurane and alfentanil (10 µg kg-1), before surgical incision, we performed three standardized tetanic stimulations (5 s, 100 Hz) of different intensities (10-30-60 mA) in a randomized order. NOL, heart rate, blood pressure and Analgesia-Nociception Index variations were assessed after each stimulation. RESULTS: Thirty children were included. Data were analyzed with a covariance pattern linear mixed regression model. NOL increased after the stimulations (p < 0.05 at each intensity). NOL response was influenced by stimulation intensity (p < 0.001). Heart rate and blood pressure were barely modified by the stimulations. Analgesia-Nociception Index decreased after the stimulations (p < 0.001 at each intensity). Analgesia-Nociception index response was not influenced by stimulation intensity (p = 0.064). NOL and Analgesia-Nociception Index responses were significantly correlated (Pearson r = 0.47; p < 0.001). CONCLUSIONS: NOL allows a quantitative assessment of nociception under anesthesia in 5-12 years-old children. This study provides a solid basis for all future investigations on NOL monitoring in pediatric anesthesia. REGISTRATION: NCT05233449.

Effect of Different Concentrations of Propofol Used as a Sole Anesthetic on Pupillary Diameter: A Randomized Trial.

BACKGROUND: Pupillometry monitoring under general anesthesia is based on the assumption that pupillary diameter variations reflect the adequacy of the provided analgesia to the intensity of the nociceptive surgical stimulus. The accurate interpretation of pupillometric data requires establishing clearly what the expected baseline unstimulated pupillary diameter at each specific level of hypnosis is. Opioids decrease pupillary diameter in a dose-dependent fashion. In contrast, the effects of hypnotic drugs on pupillary diameter are not well known. Our aim was to describe the potential relationship between propofol predicted effect-site concentrations (Cets) ranging from 1 to 3 µg/mL and pupillary diameter. METHODS: Patients were randomized to receive propofol by target-controlled infusion at a predicted Cet of 1, 2, or 3 µg/mL (groups P1, P2, and P3, respectively). Pupillary diameter measurements were performed after 10 minutes of steady-state propofol infusion at the randomized Cet. No stimulation was performed during the study. Heart rate and bispectral index (BIS) were continuously recorded. RESULTS: Forty patients were included: (13, 14, and 13 in groups P1, P2, and P3, respectively). Mean pupillary diameter was 5.7 mm (1 mm) in group P1, 4.8 mm (1.3 mm) in group P2, and 3.3 mm (0.8 mm) in group P3. Propofol had a dose-dependent effect on pupillary diameter (linear regression R = 0.45, P < .001). Pupillary diameter was positively correlated with the BIS (Spearman r = 0.75 [95% confidence interval (CI), 0.54 to -0.87] P < .001). CONCLUSIONS: From 1 to 3 µg/mL of predicted Cet, propofol has a dose-dependent effect on pupillary diameter. Within this concentrations range, there is a positive correlation between BIS and pupillary diameter. The subcortical effect of propofol on pupillary diameter is correlated to its effect on the cortex. Studies assessing pupillary diameter as a marker of the nociception-antinociception balance should be performed in patients with a standardized depth of hypnosis.

Remote peripheral tissue oxygenation does not predict postoperative free flap complications in complex head and neck cancer surgery: A prospective cohort study.

BACKGROUND: Patients undergoing free flap reconstruction after head and neck cancer may develop free flap complications. In the perioperative period, haemoglobin content and oxygen tissue saturation (StO2) measured directly on the free flap reflect peripheral tissue oxygenation. However, in this type of surgery, StO2 cannot always be applied directly or proximate to the free flap. The aim of this study was to assess the possible value of StO2 measured at the thenar eminence and other 24hour perioperative factors on free flap complications. METHODS: Inclusion criteria corresponded to patients with head and neck cancer with free flap surgery in whom direct StO2 could not be monitored on the flap nor in its peripheral area. Patient characteristics and intraoperative data, such as haemoglobin and fluid management, were prospectively collected. StO2 was measured remotely on the thenar eminence. Data were collected for 24hours and free flap complications were recorded for up to 15days after surgery. Patients were thereafter classified into two groups: with or without free flap complications and the data were compared in consequence. RESULTS: Forty consecutive patients were prospectively included. Ten patients had postoperative free flap complications and were compared to the 30 other patients without complications. The haemoglobin level at the reperfusion of the flap: (AUC 0.80 [0.65-0.91], threshold 9.9g/dL, P<0.001) and body mass index [BMI] (AUC 0.80 [0.64-0.72], threshold 24.5kg/m2, P<0.01) were significantly related to complications. CONCLUSION: In head and neck complex oncologic reconstructive surgery, haemoglobin and BMI were the most sensitive tools for predicting postoperative free flap complications, while thenar eminence StO2 was not.

Outcomes in critically ill patients with systemic rheumatic disease: a multicenter study.

BACKGROUND: Patients with systemic rheumatic diseases (SRDs) may require ICU management for SRD exacerbation or treatment-related infections or toxicities. METHODS: This was an observational study at 10 university-affiliated ICUs in France. Consecutive patients with SRDs were included. Determinants of ICU mortality were identified through multivariable logistic analysis. RESULTS: Three hundred sixty-three patients (65.3% women; median age, 59 years [interquartile range, 42-70 years]) accounted for 381 admissions. Connective tissue disease (primarily systemic lupus erythematosus) accounted for 66.1% of SRDs and systemic vasculitides for 26.2% (chiefly antineutrophil cytoplasm antibodies-associated vasculitides). SRDs were newly diagnosed in 43 cases (11.3%). Direct admission to the ICU occurred in 143 cases (37.9%). Reasons for ICU admissions were infection (39.9%), SRD exacerbation (34.4%), toxicity (5.8%), or miscellaneous (19.9%). Respiratory involvement was the leading cause of admission (56.8%), followed by shock (41.5%) and acute kidney injury (42.2%). Median Sequential Organ Failure Assessment (SOFA) score on day 1 was 5 (3-8). Mechanical ventilation was required in 57% of cases, vasopressors in 33.9%, and renal replacement therapy in 28.1%. ICU mortality rate was 21.0% (80 deaths). Factors associated with ICU mortality were shock (OR, 3.77; 95% CI, 1.93-7.36), SOFA score at day 1 (OR, 1.19; 95% CI, 1.10-1.30), and direct admission (OR, 0.52; 95% CI, 0.28-0.97). Neither comorbidities nor SRD characteristics were associated with survival. CONCLUSIONS: In patients with SRDs, critical care management is mostly needed only in patients with a previously known SRD; however, diagnosis can be made in the ICU for 12% of patients. Infection and SRD exacerbation account for more than two-thirds of these situations, both targeting chiefly the lungs. Direct admission to the ICU may improve outcomes.

Empiric/pre-emptive anti-Candida therapy in non-neutropenic ICU patients.

The potential of the systemic antifungal treatment of non-immunocompromised patients with sepsis, extra-digestive Candida colonization and multiple organ failure is unknown, although it represents three out of four antifungal treatments prescribed in intensive care units. It may allow an early treatment of invasive fungal infection at incubation phase, but exposes patients to unnecessary antifungal treatments with subsequent costs and antifungal selection pressure. As early diagnostic tests for invasive candidiasis are still considered insufficient, the potential of this strategy needs to be demonstrated by a randomized controlled trial. Such a trial is currently ongoing.

Treatment of bloodstream infections in ICUs.

Bloodstream infections (BSIs) are frequent in ICU and is a prognostic factor of severe sepsis. Community acquired BSIs usually due to susceptible bacteria should be clearly differentiated from healthcare associated BSIs frequently due to resistant hospital strains. Early adequate treatment is key and should use guidelines and direct examination of samples performed from the infectious source. Previous antibiotic therapy knowledge, history of multi-drug resistant organism (MDRO) carriage are other major determinants of first choice antimicrobials in heathcare-associated and nosocomial BSIs. Initial antimicrobial dose should be adapted to pharmacokinetic knowledge. In general, a high dose is recommended at the beginning of treatment. If MDRO is suspected combination antibiotic therapy is mandatory because it increase the spectrum of treatment. Most of time, combination should be pursued no more than 2 to 5 days.Given the negative impact of useless antimicrobials, maximal effort should be done to decrease the antibiotic selection pressure. De-escalation from a broad spectrum to a narrow spectrum antimicrobial decreases the antibiotic selection pressure without negative impact on mortality. Duration of therapy should be shortened as often as possible especially when organism is susceptible, when the infection source has been totally controlled.

Predictors of insufficient amikacin peak concentration in critically ill patients receiving a 25 mg/kg total body weight regimen.

PURPOSE: Amikacin requires pharmacodynamic targets of peak serum concentration (Cmax) of 8-10 times the minimal inhibitory concentration, corresponding to a target Cmax of 60-80 mg/L for the less susceptible bacteria. Even with new dosing regimens of 25 mg/kg, 30% of patients do not meet the pharmacodynamic target. We aimed to identify predictive factors for insufficient Cmax in a population of critically ill patients. METHODS: Prospective observational monocentric study of patients admitted to a general ICU and requiring a loading dose of amikacin. Amikacin was administered intravenously at the dose of 25 mg/kg of total body weight. Independent determinants of Cmax < 60 mg/L were identified by mixed model multivariate analysis. RESULTS: Over a 1-year period, 181 episodes in 146 patients (SAPS 2 = 51 [41-68]) were included. At inclusion, the SOFA score was 8 [6-12], 119 (66%) episodes required vasopressors, 150 (83%) mechanical ventilation, and 81 (45%) renal replacement therapy. The amikacin Cmax was 69 [54.9-84.4] mg/L. Overall, 60 (33%) episodes had a Cmax < 60 mg/L. The risk of Cmax < 60 mg/L associated with BMI < 25 kg/m(2) varied across quarters of inclusion. Independent risk factors for Cmax < 60 mg/L were a BMI < 25 kg/m(2) over the first quarter (odds ratio (OR) 15.95, 95% confidence interval (CI) [3.68-69.20], p < 0.001) and positive 24-h fluid balance (OR per 250-mL increment 1.06, 95% [CI 1.01-1.11], p = 0.018). CONCLUSIONS: Despite an amikacin dose of 25 mg/kg of total body weight, 33% of patients still had an amikacin Cmax < 60 mg/L. Positive 24-h fluid balance was identified as a predictive factor of Cmax < 60 mg/L. When total body weight is used, low BMI tended to be associated with amikacin underdosing. These results suggest the need for higher doses in patients with a positive 24-h fluid balance in order to reach adequate therapeutic targets.