Olfactory dysfunction as an early predictor for post-COVID condition at 1-year follow-up.

BACKGROUND: Olfactory dysfunction together with neurological and cognitive symptoms are common after COVID-19. We aimed to study whether performance on olfactory and neuropsychological tests following infection predict post-COVID condition (PCC), persisting symptoms, and reduced health-related quality of life. METHODS: Both hospitalized (N = 10) and non-hospitalized individuals (N = 56) were enrolled in this prospective cohort study. Participants were evaluated 1-3 months after infection with an olfactory threshold test and neuropsychological tests, which was used as predictors of PCC. A questionnaire outlining persisting symptoms and the validated instrument EuroQol five-dimension five-level for health-related quality of life assessment were used as outcome data 1 year after infection (N = 59). Principal component analysis was used to identify relevant predictors for PCC at 1 year. RESULTS: Objectively assessed olfactory dysfunction at 1-3 months post infection, but not subjective olfactory symptoms, predicted post-COVID condition with reduced health-related quality of life (PCC+) at 1 year. The PCC+ group scored more often below the cut off for mild cognitive impairment on the Montreal Cognitive Assessment (61.5% vs. 21.7%) and higher on the Multidimensional Fatigue Inventory-20, compared to the group without PCC+. CONCLUSION: Our results indicate that objectively assessed, olfactory dysfunction is a predictor for PCC+. These findings underscore the importance of objective olfactory testing. We propose that olfactory screening in the early post-acute phase of COVID-19 infection might identify individuals that are at higher risk of developing long-term health sequalae.

Cerebrovascular Pressure Reactivity Measures: Index Comparison and Clinical Outcome in Patients With Traumatic Brain Injury Treated According to an Intracranial Pressure-Focused Management: Rejection of the Null Hypothesis.

The aim was to investigate whether the pressure reactivity indices PRx, long-PRx (L-PRx), and pressure reactivity (PR) are interchangeable as measures of vascular reactivity, and whether they correlate with clinical outcome when an intracranial pressure (ICP)-targeted treatment regimen is applied in patients with traumatic brain injury (TBI). Patients with TBI (n = 29) that arrived at the hospital within 24 h of injury were included. PRx and L-PRx were derived from Pearson correlations between mean arterial pressure (MAP) and ICP over a short- and long-time interval. PR was the regression coefficient between the hourly mean values of ICP and MAP. Indices were compared to each other, parameters at admission, and outcome assessed by the extended Glasgow Outcome Scale-Extended (GOSE) at 6 and 12 months. PRx and L-PRx had the strongest correlation with each other (R = 0.536, p < 0.01). A correlation was also noted between L-PRx and PR (R = 0.475, p < 0.01), but not between PRx and PR. A correlation was found between age and PRx (R = 0.482, p = 0.01). No association with outcome for any of the indices was found. PRx/L-PRx and L-PRx/PR were moderately correlated with each other. Age was associated with PRx. None of the indices correlated with outcome when our ICP treatment regime was applied. Part of our null hypothesis, that the three indices are associated with outcome, must be rejected. There was, however, an association between some of the indices. To further understand the relation of treatment regimes and pressure reactivity indices, a larger, randomized study is warranted.

Preoperative anxiety level is not associated with postoperative negative behavioral changes in premedicated children.

BACKGROUND: Anesthesia preinduction anxiety in children can according to some studies lead to long-term anxiety and negative behavioral changes (NBC), while other studies have not found this effect. This secondary analysis from a recent premedication trial comparing clonidine and midazolam aimed to test the relation between preoperative anxiety assessed with modified Yale Preoperative Anxiety Scale (mYPAS) and postoperative NBCs assessed with Post Hospital Behavior Questionnaire (PHBQ), regardless of premedication type. METHODS: This is a planned secondary analysis from a published premedication comparison trial in an outpatient surgery cohort, children aged 2-7 years. Participant and preoperative factors, particularly preoperative anxiety as mYPAS scores, were assessed for association with development of postoperative NBCs. RESULTS: Fifty-four of the 115 participants had high preinduction anxiety (mYPAS >30), and 19 of 115 developed >3 postoperative NBCs 1 week after surgery. There was no association between preinduction anxiety level as mYPAS scores and the development of postoperative NBCs at 1 week after surgery (10 of 19 had both, p = .62) nor after 4- or 26-weeks post-surgery. Only lower age was associated with development of NBCs postoperatively. CONCLUSIONS: Based on the findings from this cohort, high preinduction anxiety does not appear to be associated with NBCs postoperatively in children premedicated with clonidine or midazolam.

Early postoperative pain as a marker of anastomotic leakage in colorectal cancer surgery.

PURPOSE: Even though anastomotic leakage after colorectal surgery is a major clinical problem in need of a timely diagnosis, early indicators of leakage have been insufficiently studied. We therefore conducted a population-based observational study to determine whether the patient's early postoperative pain is an independent marker of anastomotic leakage. METHODS: By combining the Swedish Colorectal Cancer Registry and the Swedish Perioperative Registry, we retrieved prospectively collected data on 3084 patients who underwent anastomotic colorectal surgery for cancer in 2014-2017. Postoperative pain, measured with the numerical rating scale (NRS), was considered exposure, while anastomotic leakage and reoperation due to leakage were outcomes. We performed logistic regression to evaluate associations, estimating odds ratios (ORs) and 95% confidence intervals (CIs), while multiple imputation was used to handle missing data. RESULTS: In total, 189 patients suffered from anastomotic leakage, of whom 121 patients also needed a reoperation due to leakage. Moderate or severe postoperative pain (NRS 4-10) was associated with an increased risk of anastomotic leakage (OR 1.69, 95% CI 1.21-2.38), as well as reoperation (OR 2.17, 95% CI 1.41-3.32). Severe pain (NRS 8-10) was more strongly related to leakage (OR 2.38, 95% CI 1.44-3.93). These associations were confirmed in multivariable analyses and when reoperation due to leakage was used as an outcome. CONCLUSION: In this population-based retrospective study on prospectively collected data, increased pain in the post-anaesthesia care unit is an independent marker of anastomotic leakage, possibly indicating a need for further diagnostic measures.

Refeeding syndrome: multimodal monitoring and clinical manifestation of an internal severe neurotrauma.

Refeeding syndrome (RFS) is a rare, potentially life-threatening, condition seen in malnourished patients starting refeeding. RFS may provoke seizures and acute encephalopathy and can be considered an internal severe neurotrauma in need of specific treatment. The objective was to describe course of disease, treatment and, for the first time, multimodal monitoring output in a comatose patient suffering RFS. After gastric-banding and severe weight loss, the patient initiated self-starving and was transferred to our intensive care unit (ICU) following rapid refeeding. At arrival, seizures, decrease in consciousness (GCS 7) and suspected acute encephalitis was presented. Serum albumin was 8 g/l. Intracranial pressure (ICP), invasive blood pressure and electrocardiography (ECG) were monitored. Pressure reactivity (PRx) and compliance (RAP) were calculated. The patient developed congestive heart failure, anuria and general oedema despite maximal neuro- and general ICU treatment. Global cerebral oedema and hypoperfusion areas with established ischemia were seen. ECG revealed massive cardiac arrhythmia and disturbed autonomic regulation. PRx indicated intact autoregulation (-0.06 ± 0.18, mean ± SD) and relatively normal compliance (RAP = 0.23 ± 0.13). After 15 days the clinical state was improved, and the patient returned to the primary hospital. RFS was associated with serious deviations in homeostasis, high ICP levels, ECG abnormalities, kidney and lung affections. It is of utmost importance to recognize this rare syndrome and to treat appropriately. Despite the severe clinical state, cerebral autoregulation and compensatory reserve were generally normal, questioning the applicability of indirect measurements such as PRx and RAP during neuro-intensive care treatment of RFS patients with cerebral engagement.

ICU discharge screening for prediction of new-onset physical disability-A multinational cohort study.

BACKGROUND: Methods to identify patients at risk for incomplete physical recovery after intensive care unit (ICU) stay are lacking. Our aim was to develop a method for prediction of new-onset physical disability at ICU discharge. METHODS: Multinational prospective cohort study in 10 general ICUs in Sweden, Denmark, and the Netherlands. Adult patients with an ICU stay ≥12 hours were eligible for inclusion. Sixteen candidate predictors were analyzed with logistic regression for associations with the primary outcome; new-onset physical disability 3 months post-ICU, defined as a ≥10 score reduction in the Barthel Index (BI) compared to baseline. RESULTS: Of the 572 included patients, follow-up data are available on 78% of patients alive at follow-up. The incidence of new-onset physical disability was 19%. Univariable and multivariable modeling rendered one sole predictor for the outcome: physical status at ICU discharge, assessed with the five first items of the Chelsea critical care physical assessment tool (CPAx) (odds ratio 0.87, 95% confidence interval (CI) 0.81-0.93), a higher score indicating a lower risk, with an area under the receiver operating characteristics curve of 0.68 (95% CI 0.61-0.76). Negative predictive value for a low-risk group (CPAx score >18) was 0.88, and positive predictive value for a high-risk group (CPAx score ≤18) was 0.32. CONCLUSION: The ICU discharge assessment described in this study had a moderate AUC but may be useful to rule out patients unlikely to need physical interventions post-ICU. For high-risk patients, research to determine post-ICU risk factors for an incomplete rehabilitation is mandated.

Adrenal response after trauma is affected by time after trauma and sedative/analgesic drugs.

BACKGROUND: The adrenal response in critically ill patients, including trauma victims, has been debated over the last decade. The aim of this study was to assess the early adrenal response after trauma. METHODS: Prospective, observational study of 50 trauma patients admitted to a level-1-trauma centre. Serum and saliva cortisol were followed from the accident site up to five days after trauma. Corticosteroid binding globulin (CBG), dehydroepiandrosterone (DHEA) and sulphated dehydroepiandrosterone (DHEAS) were obtained twice during the first five days after trauma. The effect of time and associations between cortisol levels and; severity of trauma, infusion of sedative/analgesic drugs, cardiovascular dysfunction and other adrenocorticotropic hormone (ACTH) dependent hormones (DHEA/DHEAS) were studied. RESULTS: There was a significant decrease over time in serum cortisol both during the initial 24 h, and from the 2nd to the 5th morning after trauma. A significant decrease over time was also observed in calculated free cortisol, DHEA, and DHEAS. No significant association was found between an injury severity score ≥ 16 (severe injury) and a low (< 200 nmol/L) serum cortisol at any time during the study period. The odds for a serum cortisol < 200 nmol/L was eight times higher in patients with continuous infusion of sedative/analgesic drugs compared to patients with no continuous infusion of sedative/analgesic drugs. CONCLUSION: Total serum cortisol, calculated free cortisol, DHEA and DHEAS decreased significantly over time after trauma. Continuous infusion of sedative/analgesic drugs was independently associated with serum cortisol < 200 nmol/L.

Saliva stimulation with glycerine and citric acid does not affect salivary cortisol levels.

OBJECTIVE: In critically ill patients with hypotension, who respond poorly to fluids and vasoactive drugs, cortisol insufficiency may be suspected. In serum over 90% of cortisol is protein-bound, thus routine measures of total serum cortisol may yield 'false lows' due to hypoproteinaemia. Thus, the occurrence of cortisol insufficiency could be overestimated in critically ill patients. Salivary cortisol can be used as a surrogate for free serum cortisol, but in critically ill patients saliva production is decreased, and insufficient volume of saliva for analysis is a common problem. The aim of this study was to investigate if a cotton-tipped applicator with glycerine and citric acid could be used for saliva stimulation without affecting salivary cortisol levels. DESIGN: Prospective, observational study. PARTICIPANTS: Thirty-six volunteers (six males, 30 females), age 49 ± 9 years, without known oral mucus membrane rupture in the mouth. MEASUREMENTS: Forty-two pairs of saliva samples (22 paired morning samples, 20 paired evening samples) were obtained before and after saliva stimulation with glycerine and citric acid. Salivary cortisol was analysed using Spectria Cortisol RIA (Orion Diagnostica, Finland). RESULTS: The paired samples correlated significantly (P < 0.0001) and there was no significant difference between un-stimulated and stimulated salivary cortisol levels. CONCLUSIONS: Saliva stimulation with a cotton-tipped applicator containing glycerine and citric acid did not significantly influence salivary cortisol levels in healthy volunteers. This indicates that salivary cortisol measurement after saliva stimulation may be a useful complement when evaluating cortisol status in critically ill patients.