Nociception assessment with videopupillometry in deeply sedated intensive care patients: Discriminative and criterion validations.

BACKGROUND: Nociceptive assessment in deeply sedated patients is challenging. Validated instruments are lacking for this unresponsive population. Videopupillometry is a promising tool but has not been established in intensive care settings. AIM/OBJECTIVE: To test the discriminate validity of pupillary dilation reflex (PDR) between non-noxious and noxious procedures for assessing nociception in non-neurological intensive care unit (ICU) patients and to test the criterion validity of pupil dilation using recommended PDR cut-off points to determine nociception. METHODS: A single-centre prospective observational study was conducted in medical-surgical ICU patients. Two independent investigators performed videopupillometer measurements during a non-noxious and a noxious procedure, once a day (up to 7 days), when the patient remained deeply sedated (Richmond Agitation-Sedation Scale score: -5 or -4). The non-noxious procedures consisted of a gentle touch on each shoulder and the noxious procedures were endotracheal suctioning or turning onto the side. Bivariable and multivariable general linear mixed models were used to account for multiple measurements in same patients. Sensitivity and specificity, and areas under the curve of the receiver operating characteristic curve were calculated. RESULTS: Sixty patients were included, and 305 sets of 3 measurements (before, during, and after), were performed. PDR was higher during noxious procedures than before (mean difference between noxious and non-noxious procedures = 31.66%). After testing all variables of patient and stimulation characteristics in bivariable models, age and noxious procedures were kept in the multivariable model. Adjusting for age, noxious procedures (coefficient = -15.14 (95% confidence interval = -20.17 to -15.52, p < 0.001) remained the only predictive factor for higher pupil change. Testing recommended cut-offs, a PDR of >12% showed a sensitivity of 65%, and a specificity of 94% for nociception prediction, with an area under the receiver operating curve of 0.828 (95% confidence interval = 0.779-0.877). CONCLUSIONS: In conclusion, PDR is a potentially appropriate measure to assess nociception in deeply sedated ICU patients, and we suggest considering its utility in daily practices. REGISTRATION: This study was not preregistered in a clinical registry. TWEETABLE ABSTRACT: Pupillometry may help clinicians to assess nociception in deeply sedated ICU patients.

Early processed electroencephalography for the monitoring of deeply sedated mechanically ventilated critically ill patients.

BACKGROUND: Deep sedation may be indicated in the intensive care unit (ICU) for the management of acute organ failure, but leads to sedative-induced delirium. Whether processed electroencephalography (p-EEG) is useful in this setting is unclear. METHODS: We conducted a single-centre observational study of non-neurological ICU patients sedated according to a standardized guideline of deep sedation (Richmond Agitation Sedation Scale [RASS] between -5 and -4) during the acute phase of respiratory and/or cardio-circulatory failure. The SedLine (Masimo Incorporated, Irvine, California) was used to monitor the Patient State Index (PSI) (ranging from 0 to 100, <25 = very deep sedation and >50 = light sedation to full awareness) during the first 72 h of care. Delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). RESULTS: The median duration of PSI monitoring was 43 h. Patients spent 49% in median of the total PSI monitoring duration with a PSI <25. Patients with delirium (n = 41/97, 42%) spent a higher percentage of total monitored time with PSI <25 (median 67% [19-91] vs. 47% [12.2-78.9]) in non-delirious patients (p .047). After adjusting for the cumulative dose of analgesia and sedation, increased time spent with PSI <25 was associated with higher delirium (odds ratio 1.014; 95% CI 1.001-1.027, p = .036). CONCLUSIONS: A clinical protocol of deep sedation targeted to RASS at the acute ICU phase may be associated with prolonged EEG suppression and increased delirium. Whether PSI-targeted sedation may help reducing sedative dose and delirium deserves further clinical investigation. RELEVANCE TO CLINICAL PRACTICE: Patients requiring deep sedation are at high risk of being over-sedated and developing delirium despite the application of an evidence-based sedation guideline. Development of early objective measures are essential to improve sedation management in these critically ill patients.

Neuromonitoring of delirium with quantitative pupillometry in sedated mechanically ventilated critically ill patients.

BACKGROUND: Intensive care unit (ICU) delirium is a frequent secondary neurological complication in critically ill patients undergoing prolonged mechanical ventilation. Quantitative pupillometry is an emerging modality for the neuromonitoring of primary acute brain injury, but its potential utility in patients at risk of ICU delirium is unknown. METHODS: This was an observational cohort study of medical-surgical ICU patients, without acute or known primary brain injury, who underwent sedation and mechanical ventilation for at least 48 h. Starting at day 3, automated infrared pupillometry-blinded to ICU caregivers-was used for repeated measurement of the pupillary function, including quantitative pupillary light reflex (q-PLR, expressed as % pupil constriction to a standardized light stimulus) and constriction velocity (CV, mm/s). The relationship between delirium, using the CAM-ICU score, and quantitative pupillary variables was examined. RESULTS: A total of 59/100 patients had ICU delirium, diagnosed at a median 8 (5-13) days from admission. Compared to non-delirious patients, subjects with ICU delirium had lower values of q-PLR (25 [19-31] vs. 20 [15-28] %) and CV (2.5 [1.7-2.8] vs. 1.7 [1.4-2.4] mm/s) at day 3, and at all additional time-points tested (p < 0.05). After adjusting for the SOFA score and the cumulative dose of analgesia and sedation, lower q-PLR was associated with an increased risk of ICU delirium (OR 1.057 [1.007-1.113] at day 3; p = 0.03). CONCLUSIONS: Sustained abnormalities of quantitative pupillary variables at the early ICU phase correlate with delirium and precede clinical diagnosis by a median 5 days. These findings suggest a potential utility of quantitative pupillometry in sedated mechanically ventilated ICU patients at high risk of delirium.

A systematic review of clinical practice guidelines and recommendations for the management of pain, sedation, delirium and iatrogenic withdrawal syndrome in pediatric intensive care.

Introduction: This systematic review aimed to evaluate the quality of clinical practice guidelines (CPGs) and recommendations for managing pain, sedation, delirium, and iatrogenic withdrawal syndrome in pediatric intensive care (PICU). The objectives included evaluating the quality of recommendations, synthesizing recommendations, harmonizing the strength of the recommendation (SoR) and the certainty of evidence (CoE), and assessing the relevance of supporting evidence. Methods: A comprehensive search in four electronic databases (Medline, Embase.com, CINAHL and JBI EBP Database), 9 guideline repositories, and 13 professional societies was conducted to identify CPGs published from January 2010 to the end of May 2023 in any language. The quality of CPGs and recommendations was assessed using the AGREE II and AGREE-REX instruments. Thematic analysis was used to synthesize recommendations, and the GRADE SoR and CoE harmonization method was used to interpret the credibility of summary recommendations. Results: A total of 18 CPGs and 170 recommendations were identified. Most CPGs were of medium-quality, and three were classified as high. A total of 30 summary recommendations were synthesized across each condition, focused on common management approaches. There was inconsistency in the SoRs and CoE for summary recommendations, those for assessment showed the highest consistency, the remaining were conditional, inconsistent, inconclusive, and lacked support from evidence. Conclusion: This systematic review provides an overview of the quality of CPGs for these four conditions in the PICU. While three CPGs achieved high-quality ratings, the overall findings reveal gaps in the evidence base of recommendations, patient and family involvement, and resources for implementation. The findings highlight the need for more rigorous and evidence-based approaches in the development and reporting of CPGs to enhance their trustworthiness. Further research is necessary to enhance the quality of recommendations for this setting. The results of this review can provide a valuable foundation for future CPG development. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=274364, PROSPERO (CRD42021274364).

Effectiveness, quality and implementation of pain, sedation, delirium, and iatrogenic withdrawal syndrome algorithms in pediatric intensive care: a systematic review and meta-analysis.

Background: Pain, sedation, delirium, and iatrogenic withdrawal syndrome are conditions that often coexist, algorithms can be used to assist healthcare professionals in decision making. However, a comprehensive review is lacking. This systematic review aimed to assess the effectiveness, quality, and implementation of algorithms for the management of pain, sedation, delirium, and iatrogenic withdrawal syndrome in all pediatric intensive care settings. Methods: A literature search was conducted on November 29, 2022, in PubMed, Embase, CINAHL and Cochrane Library, ProQuest Dissertations & Theses, and Google Scholar to identify algorithms implemented in pediatric intensive care and published since 2005. Three reviewers independently screened the records for inclusion, verified and extracted data. Included studies were assessed for risk of bias using the JBI checklists, and algorithm quality was assessed using the PROFILE tool (higher % = higher quality). Meta-analyses were performed to compare algorithms to usual care on various outcomes (length of stay, duration and cumulative dose of analgesics and sedatives, length of mechanical ventilation, and incidence of withdrawal). Results: From 6,779 records, 32 studies, including 28 algorithms, were included. The majority of algorithms (68%) focused on sedation in combination with other conditions. Risk of bias was low in 28 studies. The average overall quality score of the algorithm was 54%, with 11 (39%) scoring as high quality. Four algorithms used clinical practice guidelines during development. The use of algorithms was found to be effective in reducing length of stay (intensive care and hospital), length of mechanical ventilation, duration of analgesic and sedative medications, cumulative dose of analgesics and sedatives, and incidence of withdrawal. Implementation strategies included education and distribution of materials (95%). Supportive determinants of algorithm implementation included leadership support and buy-in, staff training, and integration into electronic health records. The fidelity to algorithm varied from 8.2% to 100%. Conclusions: The review suggests that algorithm-based management of pain, sedation and withdrawal is more effective than usual care in pediatric intensive care settings. There is a need for more rigorous use of evidence in the development of algorithms and the provision of details on the implementation process. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021276053, PROSPERO [CRD42021276053].

Delirium in Adults With COVID-19-Related Acute Respiratory Distress Syndrome: Comparison With Other Etiologies.

BACKGROUND AND OBJECTIVES: Neurologic complications have been associated with COVID-19, including delirium. Such complications have been reported to be frequent among intensive care unit (ICU)-admitted patients. We hypothesized that the rate of neurologic complications would be higher in COVID-19 associated acute respiratory distress syndrome (ARDS) than those who develop ARDS from a different cause. METHODS: We conducted a retrospective cohort study in the adult ICU of Lausanne University Hospital, including all consecutive patients fulfilling the Berlin criteria for ARDS hospitalized between December 2017 and June 2021, stratifying exposure between COVID-19 or not. The primary outcome was delirium onset during ICU stay, defined by the confusion assessment method (CAM-ICU). Exploratory outcomes included development of neurologic complications of the central nervous system (stroke, hemorrhage, and vasculitis), critical illness weakness, and 30- and 180-day all-cause mortality. RESULTS: Three hundred eleven patients were included in the study (253 with COVID-19 and 58 with other causes) and CAM-ICU could be assessed in 231 (74.3% in COVID-19 vs 74.1% in non-COVID-19). The proportion of patients developing delirium was similar in patients with COVID-19 and controls in univariate comparison (69.1% vs 60.5%, p = 0.246). Yet, patients with COVID-19 had a higher body mass index, lower ICU severity, longer mechanical ventilation, and higher sedation doses (propofol and dexmedetomidine). After adjusting for these factors in a multivariable analysis, the risk of delirium remained comparable across groups (adjusted OR [95% CI]: 0.86 [0.35-2.1]). Similarly, COVID-19-related ARDS had no effect on all-cause mortality at 30 days (adjusted OR: 0.87 [0.39-1.92]) and 180 days (adjusted OR: 0.67 [0.33-1.35]). Finally, neurologic complications affecting the CNS (adjusted OR: 1.15 [0.25-5.29]) and critical illness weakness (adjusted OR: 2.99 [0.97-9.1]) were not higher in the COVID-19 group. DISCUSSION: Compared with other etiologies, patients with COVID-19 did not have higher incidence of delirium and other neurologic complications, after accounting for underlying disease severity in patients with ARDS. Management of COVID-19-associated ARDS needed longer invasive ventilation and higher sedation, which could explain higher rates of delirium in uncontrolled studies.

Hypertonic lactate for the treatment of intracranial hypertension in patients with acute brain injury.

Hypertonic lactate (HL) is emerging as alternative treatment of intracranial hypertension following acute brain injury (ABI), but comparative studies are limited. Here, we examined the effectiveness of HL on main cerebral and systemic physiologic variables, and further compared it to that of standard hypertonic saline (HS). Retrospective cohort analysis of ABI subjects who received sequential osmotherapy with 7.5% HS followed by HL-given at equi-osmolar (2400 mOsmol/L) and isovolumic (1.5 mL/kg) bolus doses-to reduce sustained elevations of ICP (> 20 mmHg). The effect of HL on brain (intracranial pressure [ICP], brain tissue PO2 [PbtO2], cerebral microdialysis [CMD] glucose and lactate/pyruvate ratio [LPR]) and blood (chloride, pH) variables was examined at different time-points (30, 60, 90, 120 min vs. baseline), and compared to that of HS. A total of 34 treatments among 17 consecutive subjects (13 traumatic brain injury [TBI], 4 non-TBI) were studied. Both agents significantly reduced ICP (p < 0.001, at all time-points tested): when comparing treatment effectiveness, absolute ICP decrease in mmHg and the duration of treatment effect (median time with ICP < 20 mmHg following osmotherapy 183 [108-257] vs. 150 [111-419] min) did not differ significantly between HL and HS (all p > 0.2). None of the treatment had statistically significant effects on PbtO2 and CMD biomarkers. Treatment with HL did not cause hyperchloremia and resulted in a more favourable systemic chloride balance than HS (Δ blood chloride - 1 ± 2.5 vs. + 4 ± 3 mmol/L; p < 0.001). This is the first clinical study showing that HL has comparative effectiveness than HS for the treatment of intracranial hypertension, while at the same time avoiding hyperchloremic acidosis. Both agents had no significant effect on cerebral oxygenation and metabolism.

Metabolic and Nutritional Characteristics of Long-Stay Critically Ill Patients.

BACKGROUND: insufficient feeding is frequent in the intensive care unit (ICU), which results in poor outcomes. Little is known about the nutrition pattern of patients requiring prolonged ICU stays. The aims of our study are to describe the demographic, metabolic, and nutritional specificities of chronically critically ill (CCI) patients defined by an ICU stay >2 weeks, and to identify an early risk factor. METHODS: analysis of consecutive patients prospectively admitted to the CCI program, with the following variables: demographic characteristics, Nutrition Risk Screening (NRS-2002) score, total daily energy from nutritional and non-nutritional sources, protein and glucose intakes, all arterial blood glucose values, length of ICU and hospital stay, and outcome (ICU and 90-day survival). Two phases were considered for the analysis: the first 10 days, and the next 20 days of the ICU stay. STATISTICS: parametric and non-parametric tests. RESULTS: 150 patients, aged 60 ± 15 years were prospectively included. Median (Q1, Q3) length of ICU stay was 31 (26, 46) days. The mortality was 18% at ICU discharge and 35.3% at 90 days. Non-survivors were older (p = 0.024), tended to have a higher SAPSII score (p = 0.072), with a significantly higher NRS score (p = 0.033). Enteral nutrition predominated, while combined feeding was minimally used. All patients received energy and protein below the ICU's protocol recommendation. The proportion of days with fasting was 10.8%, being significantly higher in non-survivors (2 versus 3 days; p = 0.038). Higher protein delivery was associated with an increase in prealbumin over time (r2 = 0.19, p = 0.027). CONCLUSIONS: High NRS scores may identify patients at highest risk of poor outcome when exposed to underfeeding. Further studies are required to evaluate a nutrition strategy for patients with high NRS, addressing combined parenteral nutrition and protein delivery.