Postoperative cognitive dysfunction: Review of pathophysiology, diagnostics and preventive strategies.

Postoperative cognitive impairment is a common disorder after major surgery. Advances in medicine and treatment have resulted in an increasingly ageing population undergoing major surgical procedures. Since age is the most important risk factor for postoperative cognitive decline, it is not surprising that impairment of cognitive functions after surgery was recorded in almost a third of elderly patients. Postoperative cognitive dysfunction is part of the spectrum of postoperative cognitive impairment and researchers often confuse it with postoperative delirium and delayed neurocognitive recovery. This is the cause of great differences in the results of research that is focused on the incidence and possible prevention of postoperative cognitive dysfunction. In this review, we focused on current recommendations for a uniform nomenclature of postoperative cognitive impairment and diagnosis of postoperative cognitive dysfunction, the presumed pathophysiology of postoperative cognitive dysfunction and recommendations for its treatment and possible prevention strategies.

Ventilation Management in a Patient with Ventilation-Perfusion Mismatch in the Early Phase of Lung Injury and during the Recovery.

Chest trauma is one of the most serious and difficult injuries, with various complications that can lead to ventilation-perfusion (V/Q) mismatch and systemic hypoxia. We are presenting a case of a 53-year-old male with no chronic therapy who was admitted to the Intensive Care Unit due to severe respiratory failure after chest trauma. He developed a right-sided pneumothorax, and then a thoracic drain was placed. On admission, the patient was hemodynamically unstable and tachypneic. He was intubated and mechanically ventilated, febrile (38.9 °C) and unconscious. A lung CT showed massive non-ventilated areas, predominantly in the right lung, guiding repeated therapeutic and diagnostic bronchoalveolar lavages. He was ventilated with PEEP of 10 cmH2O with a FiO2 of 0.6-0.8. Empirical broad-spectrum antimicrobial therapy was immediately initiated. Both high FiO2 and moderate PEEP were maintained and adjusted according to the current blood gas values and oxygen saturation. He was weaned from mechanical ventilation, and non-invasive oxygenation was continued. After Stenotrophomonas maltophilia was identified and treated with sulfamethoxazole/trimethoprim, a regression of lung infiltrates was observed. In conclusion, both ventilatory and antibiotic therapy were needed to improve the oxygenation and outcome of the patient with S. maltophilia pneumonia and V/Q mismatch.

Corrigendum: Different pharmacokinetics of tramadol, O-demethyltramadol and N-demethyltramadol in postoperative surgical patients from those observed in medical patients.

[This corrects the article DOI: 10.3389/fphar.2021.656748.].

The COVID-19 Pandemic and Elective Spine Surgery-A Single Center Experience.

Background and objective: The COVID-19 pandemic had a profound impact on medical practice worldwide. In this study, we aimed to investigate the trends of elective spine surgery in our department before and during the pandemic. Materials and methods: Total number of spine procedures due to disc herniation (DH) or spinal stenosis (SS) was collected during 2019-2021 in the Department of Neurosurgery, University Hospital Center Osijek, Croatia. In order to elucidate potential risk factors in the post-pandemic period, demographic data were collected for patients who underwent surgery during 2021. Results: In 2020, there was a 22.1% decrease in the number of surgeries compared to 2019 (205 vs. 263), but during 2021 we observed an increase of 36.1% compared to 2020 (279 vs. 205). The mean age of patients in 2021 was 53.14 years (53.14 ± 13.05) with body mass index of 28.31 kg/m2 (28.31 ± 4.89). There were 179 overweight patients (74%) and 103 smokers (42.6%). Although male and female patients were equally represented (121 each), there was a significant interaction of weight class and sex (p = 0.013). Patients younger than 65 were more likely to undergo surgery due to DH (p < 0.001), whereas older patients were more likely to suffer from SS (p < 0.001). Conclusions: The volume of elective spine surgeries decreased in the first year of the pandemic and increased the following year. Our results suggest that public health policies in the early pandemic period reduced elective surgical procedures, which was followed by a compensatory increase in the following period.

Long-Term Outcomes of Breast Cancer Patients Receiving Levobupivacaine Wound Infiltration or Diclofenac for Postoperative Pain Relief.

Breast cancer is the most common malignant disease in women. Preclinical studies have confirmed that the local anesthetic levobupivacaine has a cytotoxic effect on breast cancer cells. We examined whether postoperative wound infiltration with levobupivacaine influences survival in 120 patients who were operated on for breast cancer and underwent quadrantectomy or mastectomy with axillary lymph node dissection. Groups with continuous levobupivacaine wound infiltration, bolus wound infiltration, and diclofenac analgesia were compared. Long-term outcomes examined were quality of life, shoulder disability, and hand grip strength (HGS) after one year and survival after 5 and 10 years. Groups that had infiltration analgesia had better shoulder function compared to diclofenac after one year. The levobupivacaine PCA group had the best-preserved HGS after 1 year (P = 0.022). The most significant predictor of the 5-year outcome was HGS (P = 0.03). Survival at 10 years was 85%, 92%, and 77% in the diclofenac, levobupivacaine bolus, and levobupivacaine PCA groups (ns. P = 0.36). The extent of the disease at the time of surgery is the most important predictor of long-term survival (P = 0.03). A larger prospective clinical study could better confirm the effect of levobupivacaine wound infiltration on outcomes after breast cancer surgery observed in this pilot study-trial number NCT05829707.

Advances in Analgosedation and Periprocedural Care for Gastrointestinal Endoscopy.

The number and complexity of endoscopic gastrointestinal diagnostic and therapeutic procedures is globally increasing. Procedural analgosedation during gastrointestinal endoscopic procedures has become the gold standard of gastrointestinal endoscopies. Patient satisfaction and safety are important for the quality of the technique. Currently there are no uniform sedation guidelines and protocols for specific gastrointestinal endoscopic procedures, and there are several challenges surrounding the choice of an appropriate analgosedation technique. These include categories of patients, choice of drug, appropriate monitoring, and medical staff providing the service. The ideal analgosedation technique should enable the satisfaction of the patient, their maximum safety and, at the same time, cost-effectiveness. Although propofol is the gold standard and the most used general anesthetic for endoscopies, its use is not without risks such as pain at the injection site, respiratory depression, and hypotension. New studies are looking for alternatives to propofol, and drugs like remimazolam and ciprofol are in the focus of researchers' interest. New monitoring techniques are also associated with them. The optimal technique of analgosedation should provide good analgesia and sedation, fast recovery, comfort for the endoscopist, patients' safety, and will have financial benefits. The future will show whether these new drugs have succeeded in these goals.

Effectiveness of Epidural Steroid Injection Depending on Discoradicular Contact: A Prospective Randomized Trial.

Lumbar radicular pain is a major public health and economic problem. It is among the most common reasons for professional disability. The most common cause of lumbar radicular pain is intervertebral disc herniation, which results from degenerative disc changes. The dominant pain mechanisms are direct pressure of the hernia on the nerve root and the local inflammatory process triggered by intervertebral disc herniation. Treatment of lumbar radicular pain includes conservative, minimally invasive, and surgical treatment. The number of minimally invasive procedures is constantly increasing, and among these methods is epidural administration of steroids and local anesthetic through a transforaminal approach (ESI TF). The aim of this research was to examine the effectiveness of ESI TF as measured by a visual analog scale (VAS) and the Oswestry Disability Index (ODI), depending on whether there is contact between the herniated intervertebral disc and the nerve root. In both groups of participants, there was a significant reduction in pain intensity, but there was no significant difference between the groups. In the group with disc herniation and nerve root contact, the only significant reduction was in pain intensity (p < 0.001). There were no significant differences in measurements in other domains of the ODI. In the group without disc herniation and nerve contact, there was a significant difference in all domains except weight lifting. In the group without contact, there was significant improvement after 1 month (p = 0.001) and 3 months (p < 0.001) according to the ODI, while there was no significant improvement in the group with contact. In addition, there were no significant differences in the distribution of participants based on the ODI and whether disc herniation and nerve contact was present. The results suggest that transforaminal epidural administration of steroids is a clinically effective method for treating lumbar radicular pain caused by intervertebral disc herniation in people with and without nerve root contact, without significant differences.

POINT-OF-CARE DIAGNOSTIC APPROACH IN A CRITICALLY ILL PATIENT WITH SEVERE BLEEDING FROM URINARY TRACT.

Coagulation disorders in critically ill patients presenting with bleeding can be multicausal. The drugs applied can interfere and impair the coagulation cascade. Point-of-care (POC) coagulation assays may resolve difficult therapeutic situations in critical illness. We report on a 73-year-old critically ill male patient with massive hematuria after bladder lithotripsy. The patient was on low molecular weight heparin therapy due to recent pulmonary embolism. He was subjected to repeated surgical hemostasis which was ineffective despite massive transfusion protocol and normal standard coagulation profile. Additional POC coagulation assays were obtained and were indicative of platelet dysfunction. We revised his medical therapy and suspected the possible drug influence on platelet aggregation. After discontinuation of target drug, platelet aggregation increased whereas hematuria stopped. Coagulation disorders in intensive care unit patients are often multifactorial. Standard laboratory tests are unreliable in complex refractory bleeding and may result in inappropriate therapeutic decisions. Stepwise approach with assessment of clinical parameters, present therapy, and a combination of POC coagulation tests is the key to optimal therapeutic management.

Predictive role of selected biomarkers in differentiating gram-positive from gram-negative sepsis in surgical patients: a retrospective study.

INTRODUCTION: Patients after major surgery are at high risk of developing sepsis, which is accompanied by elevated serum levels of C-reactive protein (CRP) and procalcitonin (PCT). This study aimed to examine the differences in serum biomarker levels concerning the causative agent of sepsis in surgical patients. MATERIAL AND METHODS: A retrospective study was carried out in the surgical intensive care unit (ICU) and included 81 septic patients admitted from January 2019 to May 2022, who had positive blood cultures (BC). Serum levels of PCT, CRP, white blood cells (WBC) and platelet counts were recorded on the day of the positive BC and over the following 3 days. RESULTS: Patients with gram(-) sepsis had significantly higher PCT levels, and lower platelet count compared to patients with gram(+) sepsis. High PCT and low platelets levels in all measurements were a significant predictor of gram(-) isolate with the highest predictive value on the third day after BC sampling, with AUROC 0.821 (95% CI: 0.692-0.950), P = 0.001, and AUROC 0.676 (95% CI: 0.541-0.811), P = 0.02, respectively. In multivariate logistic regression, platelets the day after BC sampling and PCT on the third day made a significant contribution in distinguishing gam(+) from gram(-) BC. Age and high serum CRP levels were significant predictors of poor outcomes. CONCLUSIONS: PCT and platelets may be useful biomarkers for predicting the causative agent of sepsis in surgical patients.

ANALGESIC EFFECT OF TRAMADOL IS NOT ALTERED BY POSTOPERATIVE SYSTEMIC INFLAMMATION AFTER MAJOR ABDOMINAL SURGERY.

Tramadol is a commonly used analgesic in intensive care units (ICUs) for acute postoperative pain. Conversion of tramadol into active metabolites may be impaired in inflammatory states. Catechol-O-methyltransferase may influence pain. The aim of the study was to examine differences in the analgesic effect of tramadol between ICU patients with and without signs of systemic inflammation. Forty-three patients were admitted to ICU after a major abdominal surgery. The patients received a dose of 100 mg of tramadol intravenously every 6 hours during the first 24 hours after surgical procedure. Pain scores were measured by the Numeric Rating Scale before and 30 minutes after tramadol administration in awake patients. Systemic inflammation was considered when at least two of the following postoperative parameters were present in the first 24 hours of ICU admission: fever or hypothermia, tachycardia, pCO2 <4.3 kPa, white blood cells >12000/mm3 or <4000/mm3, or preoperative value of C-reactive protein (CRP) >50 mg/L or/and procalcitonin (PCT) >0.5 mg/L. Catechol-O-methyltransferase was analyzed postoperatively. Fifteen (34.8%) patients met the criteria for systemic inflammation. Tramadol was proven to be an effective analgesic for the treatment of postoperative pain regardless of the presence of systemic inflammation (p<0.05). Lower perception of pain before tramadol application was observed in patients with systemic inflammation, but the difference was not significant. A negative correlation was observed between the preoperative values of CRP and PCT and the analgesic effect of tramadol assessed at the second measurement point (r=-0.358, p=0.03, and r=-0.364, p=0.02, respectively). Catechol-O-methyltransferase variants were not in correlation with pain and opioid consumption. Based on our findings, tramadol is effective in lowering pain scores after major abdominal surgery irrespective of the presence of systemic inflammation.

Different Pharmacokinetics of Tramadol, O-Demethyltramadol and N-Demethyltramadol in Postoperative Surgical Patients From Those Observed in Medical Patients.

Background: Most studies examining tramadol metabolism have been carried out in non-surgical patients and with oral tramadol. The aim of this study was 1) to measure concentrations of tramadol, O-demethyltramadol (ODT), and N-demethyltramadol (NDT) in the surgical patients admitted to the intensive care unit (ICU) within the first 24 postoperative hours after intravenous application of tramadol, and 2) to examine the effect of systemic inflammation on tramadol metabolism and postoperative pain. Methods: A prospective observational study was carried out in the surgical ICU in the tertiary hospital. In the group of 47 subsequent patients undergoing major abdominal surgery, pre-operative blood samples were taken for CYP2D6 polymorphism analysis. Systemic inflammation was assessed based on laboratory and clinical indicators. All patients received 100 mg of tramadol intravenously every 6 h during the first postoperative day. Postoperative pain was assessed before and 30 min after tramadol injections. Tramadol, ODT, and NDT concentrations were determined by high-performance liquid chromatography. Results: CYP2D6 analysis revealed 2 poor (PM), 22 intermediate (IM), 22 extensive (EM), and 1 ultrafast metabolizer. After a dose of 100 mg of tramadol, t1/2 of 4.8 (3.2-7.6) h was observed. There were no differences in tramadol concentration among metabolic phenotypes. The area under the concentration-time curve at the first dose interval (AUC1-6) of tramadol was 1,200 (917.9-1944.4) µg ×h ×L-1. NDT concentrations in UM were below the limit of quantification until the second dose of tramadol was administrated, while PM had higher NDT concentrations compared to EM and IM. ODT concentrations were higher in EM, compared to IM and PM. ODT AUC1-6 was 229.6 (137.7-326.2) µg ×h ×L-1 and 95.5 (49.1-204.3) µg ×h ×L-1 in EM and IM, respectively (p = 0.004). Preoperative cholinesterase activity (ChE) of ≤4244 U L-1 was a cut-off value for a prediction of systemic inflammation in an early postoperative period. NDT AUC1-6 were significantly higher in patients with low ChE compared with normal ChE patients (p = 0.006). Pain measurements have confirmed that sufficient pain control was achieved in all patients after the second tramadol dose, except in the PM. Conclusions: CYP2D6 polymorphism is a major factor in O-demethylation, while systemic inflammation accompanied by low ChE has an important role in the N-demethylation of tramadol in postoperative patients. Concentrations of tramadol, ODT, and NDT are lower in surgical patients than previously reported in non-surgical patients. Clinical Trial Registration: ClinicalTrials.gov, NCT04004481.

The Influence of Depression, Anxiety and Stress on Changes in Locomotor Parameters in Patients Who Are Prone to Develop COPD.

BACKGROUND: Depression and anxiety are the most prevalent diseases that contribute to global disability, especially if they are not early recognised and properly treated. They occur as part of many chronic diseases, often remain unrecognised at an early stage, and significantly contribute to the progression of the underlying disease reducing the quality of life in these patients. Numerous studies have shown that anxiety / depression and dyspnea are the leading symptoms in patients with COPD that are associated with high morbidity and mortality. The aim of this study was to determine the relationship between the degree of depression, anxiety and stress, using DASS- 21 scale, and changes in locomotor parameters in smokers who are prone to develop COPD. SUBJECTS AND METHODS: The study included 164 patients, smokers and non-smokers, who underwent spirometry, 6-minute walk test and bicycle ergometer. They were all measured for body weight, height, waist circumference, pulse, blood pressure and each patient completed DASS-21, CAT and IPAQ questionnaire. RESULTS: The results of the IPAQ questionnaire indicated a statistically significant difference in the physical activity of smokers and non-smokers. A statistically significant was found between DASS-21 and patients physical activity (p=0.0001), 6-minute walk test (r=-0.186, p=0.017), VO2 max (r=-0.220, p=0.005) and weekly calorie consumption (r=-0.222, p=0.004). CONCLUSION: According to the results of the study, an increased degree of anxiety, depression and stress is an important factor influencing changes in locomotor parameters in smokers who are prone to develop COPD.

Influence of postoperative analgesia on systemic inflammatory response and postoperative cognitive dysfunction after femoral fractures surgery: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: To investigate the possible effect of postoperatively applied analgesics-epidurally applied levobupivacaine or intravenously applied morphine-on systemic inflammatory response and plasma concentration of interleukin (IL)-6 and to determine whether the intensity of inflammatory response is related to postoperative cognitive dysfunction (POCD). METHODS: This is a randomized, prospective, controlled study in an academic hospital. Patients were 65 years and older scheduled for femoral fracture fixation from July 2016 to September 2017. Inflammatory response was assessed by leukocytes, neutrophils, C reactive protein (CRP) and fibrinogen levels in four blood samples (before anesthesia, 24 hours, 72 hours and 120 hours postoperatively) and IL-6 concentration from three blood samples (before anesthesia, 24 hours and 72 hours postoperatively). Cognitive function was assessed using the Mini-Mental State Examination preoperatively, from the first to the fifth postoperative day and on the day of discharge. RESULTS: The study population included 70 patients, 35 in each group. The incidence of POCD was significantly lower in the levobupivacaine group (9%) than in the morphine group (31%) (p=0.03). CRP was significantly lower in the levobupivacaine group 72 hours (p=0.03) and 120 hours (p=0.04) after surgery. IL-6 values were significantly lower in the levobupivacaine group 72 hours after surgery (p=0.02). The only predictor of POCD in all patients was the level of IL-6 72 hours after surgery (p=0.03). CONCLUSIONS: There is a statistically significant association between use of epidural levobupivacaine and a reduction in some inflammatory markers. Postoperative patient-controlled epidural analgesia reduces the incidence of POCD compared with intravenous morphine analgesia in the studied population. TRIAL REGISTRATION NUMBER: NCT02848599.