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Background and Objective The risk of thrombotic complications in critical patients with COVID-19 remains extremely high, and multicenter trials failed to prove a survival benefit of escalated doses of low-molecular-weight heparins (nadroparin calcium) in this group. The aim of this study was to develop a pharmacokinetic model of nadroparin according to different stages of COVID-19 severity. Methods Blood samples were obtained from 43 patients with COVID-19 who received nadroparin and were treated with conventional oxygen therapy, mechanical ventilation, and extracorporeal membrane oxygenation. We recorded clinical, biochemical, and hemodynamic variables during 72 h of treatment. The analyzed data comprised 782 serum nadroparin concentrations and 219 anti-Xa levels. We conducted population nonlinear mixed-effects modeling (NONMEM) and performed Monte Carlo simulations of the probability of target attainment for reaching 0.2–0.5 IU/mL anti-Xa levels in study groups. Results We successfully developed a one-compartment model to describe the population pharmacokinetics of nadroparin in different stages of COVID-19. The absorption rate constant of nadroparin was 3.8 and 3.2 times lower, concentration clearance was 2.22 and 2.93 times higher, and anti-Xa clearance was 0.87 and 1.1 times higher in mechanically ventilated patients and the extracorporeal membrane oxygenation group compared with patients treated with conventional oxygen, respectively. The newly developed model indicated that 5.900 IU of nadroparin given subcutaneously twice daily in the mechanically ventilated patients led to a similar probability of target attainment of 90% as 5.900 IU of subcutaneous nadroparin given once daily in the group supplemented with conventional oxygen. Conclusions Different nadroparin dosing is required for patients undergoing mechanical ventilation and extracorporeal membrane oxygenation to achieve the same targets as those for non-critically ill patients. Clinical Trial Registration ClinicalTrials.gov identifier no. NCT05621915.

Background: Renal replacement therapy (RRT), widely used in the treatment of renal injury during sepsis, aims to eliminate the toxins and proinflammatory cytokines involved in the pathomechanism underlying septic shock. Dialysis filters are characterized by a high adsorption potential for cytokines in RRT in the case of septic renal injury. For the treatment of sepsis with antibiotics, it is of key importance to achieve the desired values of PK/PD indices. Continuous renal replacement therapy (CRRT) may affect antimicrobial clearance, increasing their elimination in some cases. Methods: The aim of this study was to determine the degree of adsorption for linezolid on three different types of filters used in CRRT. In our in vitro study, a continuous veno-venous hemofiltration (CVVH) was conducted using three types of filters: polysulfone (PS), polyethyleneimine-treated polyacrylonitrile (PAN PEI), and non-PEI-treated polyacrylonitrile (PAN). Each type of filter was used in three CVVH cycles, involving the use of 600 mg of linezolid dissolved in 700 mL of bovine blood or in 700 mL of 0.9% NaCl. In each case, the total volume of the obtained solution was 1000 mL. Blood samples were collected at particular time points to measure their drug concentration. The differences in mean drug/NaCl adsorption and drug/blood adsorption were determined using a one-way ANOVA with multiple comparisons via Tukey’s post hoc test; a p-value of <0.05 was considered significant. Results: A significant adsorption of linezolid was found for PAN PEI filters, both in samples obtained from bovine blood and 0.9% NaCl solutions, at the endpoint. In PAN PEI samples, the concentration of linezolid in 0.9% NaCl solutions decreased from 594.74 μg/mL to 310.66 μg/mL after 120 min (the difference was established at 52%). In blood samples, the initial concentration was 495.18 μg/mL, which then decreased to 359.84 μg/mL (73% of the beginning value). No significant adsorption was demonstrated on PAN or PS filters. Conclusion: There is a need for in vivo research to confirm the effect of filter type on linezolid concentration in patients undergoing CRRT.

Severe postoperative pain affects most patients after thoracotomy and is a risk factor for post-thoracotomy pain syndrome (PTPS). This randomized controlled trial compared preemptively administered ketamine versus continuous paravertebral block (PVB) versus control in patients undergoing posterolateral thoracotomy. The primary outcome was acute pain intensity on the visual analog scale (VAS) on the first postoperative day. Secondary outcomes included morphine consumption, patient satisfaction, and PTPS assessment with Neuropathic Pain Syndrome Inventory (NPSI). Acute pain intensity was significantly lower with PVB compared to other groups at four out of six time points. Patients in the PVB group used significantly less morphine via a patient-controlled analgesia pump than participants in other groups. Moreover, patients were more satisfied with postoperative pain management after PVB. PVB, but not ketamine, decreased PTPS intensity at 1, 3, and 6 months after posterolateral thoracotomy. Acute pain intensity at hour 8 and PTPS intensity at month 3 correlated positively with PTPS at month 6. Bodyweight was negatively associated with chronic pain at month 6. Thus, PVB but not preemptively administered ketamine decreases both acute and chronic pain intensity following posterolateral thoracotomies.

Background The erector spinae plane (ESP) block has recently been shown to effectively alleviate postoperative pain and reduce opioid consumption in breast surgery patients. However, data are still limited concerning the quality of recovery in patients following this procedure. Methods This study was a randomized controlled trial (RCT) performed in a university hospital. We randomly allocated patients to one of three groups: ESP, SHAM, and control (CON). Procedures in the ESP and SHAM blocks were performed ipsilaterally with 0.375% ropivacaine or 0.9% saline (0.4 mL/kg). Our primary outcome was the assessment of the patient’s improvement with quality-of-recovery 40 (QoR-40) a day after surgery. Other outcome assessments included postoperative pain evaluation on the visual analog scale (VAS), 24-hour opioid consumption with patient-controlled analgesia (PCA), time to the first opioid demand, and global satisfaction with perioperative treatment. Results Overall, patients in the ESP group had improved QoR-40 compared to the CON group, 186 [177–193] vs. 175 [165–183] (medians and interquartile ranges). Pain severity was significantly higher in the CON group compared to the ESP group at hours 2 (38 [23–53] vs. 20 [7–32]) and 4 (30 [18–51] vs. 19 [7–25]). Moreover, we observed lower oxycodone consumption after 24 hours with the PCA pump between the ESP (4 [2–8] mg) and the CON (9.5 [5–19]) groups. Patients in the CON group used PCA sooner than those in the ESP group. Participants in the ESP group were more satisfied with treatment than those in the CON group. We found no statistical difference between SHAM and the other groups. Conclusions Compared to the CON group, the ESP block improved the quality of recovery, alleviated pain intensity, and lowered opioid consumption in patients undergoing breast surgery. However, we did not observe this superiority in comparison with the SHAM group. Trial registration NCT04726878 .

Background: Severe postoperative pain is a significant problem after cesarean sections. Methods: This study was a randomized, controlled trial of 105 patients conducted in two hospitals. All patients were anesthetized spinally for elective cesarean section. Each participant was randomly allocated to one of three study groups: the quadratus lumborum block (QLB) group, the transversus abdominis plane block (TAPB) group, or the control (CON) group. The primary outcome of this study determined acute pain intensity on the visual analog scale (VAS). The secondary outcomes determined morphine consumption and chronic pain evaluation according to the Neuropathic Pain Symptom Inventory (NPSI) after hospital discharge. Results: At rest, the pain intensity was significantly higher in the CON group than in the QLB and TAPB groups at hours two and eight. Upon activity, the pain in the control subjects was more severe than in the QLB and TAPB groups in three and two of five measurements, respectively. Moreover, morphine consumption was significantly lower in the QLB (9 (5–10)) and TAPB (10 (6–14)) groups than in the CON (16 (11–19)) group. Persistent postoperative pain was significantly lower in the QLB group than in the CON group at months one and six following hospital discharge. Conclusions: Both the QLB and TAPB can improve pain management after cesarean delivery. Moreover, the QLB might reduce the severity of persistent postoperative pain months after cesarean section.

Kynurenic acid (KYNA) is an endogenous compound with a multidirectional effect. It possesses antiapoptotic, anti-inflammatory, and antioxidative properties that may be beneficial in the treatment of corneal injuries. Moreover, KYNA has been used successfully to improve the healing outcome of skin wounds. The aim of the present study is to evaluate the effects of KYNA on corneal and conjunctival cells in vitro and the re-epithelization of corneal erosion in rabbits in vivo. Normal human corneal epithelial cell (10.014 pRSV-T) and conjunctival epithelial cell (HC0597) lines were used. Cellular metabolism, cell viability, transwell migration, and the secretion of IL-1β, IL-6, and IL-10 were determined. In rabbits, after corneal de-epithelization, eye drops containing 0.002% and 1% KYNA were applied five times a day until full recovery. KYNA decreased metabolism but did not affect the proliferation of the corneal epithelium. It decreased both the metabolism and proliferation of conjunctival epithelium. KYNA enhanced the migration of corneal but not conjunctival epithelial cells. KYNA reduced the secretion of IL-1β and IL-6 from the corneal epithelium, leaving IL-10 secretion unaffected. The release of all studied cytokines from the conjunctival epithelium exposed to KYNA was unchanged. KYNA at higher concentration accelerated the healing of the corneal epithelium. These favorable properties of KYNA suggest that KYNA containing topical pharmaceutical products can be used in the treatment of ocular surface diseases.

Multiple major health organisations recommend the use of extracorporeal membrane oxygenation (ECMO) support for COVID-19-related acute hypoxaemic respiratory failure. However, initial reports of ECMO use in patients with COVID-19 described very high mortality and there have been no large, international cohort studies of ECMO for COVID-19 reported to date. We used data from the Extracorporeal Life Support Organization (ELSO) Registry to characterise the epidemiology, hospital course, and outcomes of patients aged 16 years or older with confirmed COVID-19 who had ECMO support initiated between Jan 16 and May 1, 2020, at 213 hospitals in 36 countries. The primary outcome was in-hospital death in a time-to-event analysis assessed at 90 days after ECMO initiation. We applied a multivariable Cox model to examine whether patient and hospital factors were associated with in-hospital mortality. Data for 1035 patients with COVID-19 who received ECMO support were included in this study. Of these, 67 (6%) remained hospitalised, 311 (30%) were discharged home or to an acute rehabilitation centre, 101 (10%) were discharged to a long-term acute care centre or unspecified location, 176 (17%) were discharged to another hospital, and 380 (37%) died. The estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 37·4% (95% CI 34·4–40·4). Mortality was 39% (380 of 968) in patients with a final disposition of death or hospital discharge. The use of ECMO for circulatory support was independently associated with higher in-hospital mortality (hazard ratio 1·89, 95% CI 1·20–2·97). In the subset of patients with COVID-19 receiving respiratory (venovenous) ECMO and characterised as having acute respiratory distress syndrome, the estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 38·0% (95% CI 34·6–41·5). In patients with COVID-19 who received ECMO, both estimated mortality 90 days after ECMO and mortality in those with a final disposition of death or discharge were less than 40%. These data from 213 hospitals worldwide provide a generalisable estimate of ECMO mortality in the setting of COVID-19. None.

Although nutritional-risk scoring systems allow the determination of the patient’s malnutrition at admission, additional tools might be useful in some clinical scenarios. Previous medical history could be unavailable in unconscious or demented patients. This study aimed to assess the ketone bodies serum levels in patients undergoing elective surgeries and to determine the possible correlation between ketone bodies serum levels and preoperative body weight loss. The study included 21 patients who underwent elective surgery. Hyperketonemia, defined as ketone bodies over 1 mmol/L, was observed in seven (33.3%) patients. Patients with hyperketonemia had significantly higher preoperative percentage body weight loss (p = 0.04) and higher nutritional risk scores prior to surgery (p = 0.04). Serum glucose and the percentage of body weight loss were associated with increased ketone bodies serum levels (Odds Ratios: 0.978 (0.961–0.996, p = 0.019) and 1.222 (1.0–1.492, p = 0.05), respectively). A significant linear correlation was found between the percentage of body weight loss and both ketones bodies (r2 = 0.25, p = 0.02) and albumin serum levels (r2 = 0.19, p = 0.04). Our study’s results might suggest a positive association between preoperative body weight loss and ketone bodies serum levels. The observation between increased ketone bodies serum levels in patients and preoperative body mass loss merits further research.

Background Current pain assessment and treatment does not address every patient’s requirements. Although the Polish national guidelines for post-operative pain management have been published, many patients experience severe pain in the postoperative period. The main goal of our study was to assess pain severity among patients from different types of hospitals (primary, secondary, and tertiary centers) after similar types of surgeries. We also aimed to determine if there were any differences in pain severity associated with anesthesia technique, type of surgery, and the patient’s age and sex. Methods This was a prospective, observational study. A questionnaire form was used to collect demographic data, type of hospital, surgery, anesthesia, and patient satisfaction of pain control in the postoperative period. The visual analogue scale (VAS) was used to measure pain severity at four time points after surgery (4, 8, 12, and 24 h). Results The study was conducted from November 2015 to June 2016 in seven hospitals in Eastern Poland, and 269 women and 293 men participated. At the 4-h measurement, 39.32% of patients assessed the pain as moderate and 19.75% as severe. A difference was found in pain intensity between patients treated in primary and secondary hospitals. Vascular surgery patients had the lowest pain intensity (19 (13–26)), especially in comparison to those undergoing thoracic surgery (30 (27–33)). A sudden elevation in pain severity among patients anesthetized with single-shot spinal technique was observed. Only 4.9% of participants received strong opioids during the first 24 h after surgery. Conclusions Postoperative pain control seems to be unexpectedly poor after single-shot subarachnoid anesthesia. Despite concerns, the use of analgesics may be insufficient in some groups of patients. Our study indicates new variables that influence the severity of pain, such as operated region, anesthetic technique, and type of surgical department. The results obtained in our study are in discrepancy with recommendations presented by the national guidelines for post-operative pain management.

Up to 56% of patients develop chronic postsurgical pain (CPSP) after coronary artery bypass grafting (CABG). CPSP can affect patients’ moods and decrease daily activities. The primary aim of this study was to investigate CPSP severity in patients following off-pump (OP) CABG using the Neuropathic Pain Symptom Inventory (NPSI). This was a prospective cohort study conducted in a cardiac surgery department of a teaching hospital. Patients undergoing OP-CABG were enrolled in an erector spinae plane block (ESPB) group (n = 27) or a control (CON) group (n = 24). Before the induction of general anesthesia, ESPB was performed on both sides under ultrasound guidance using 0.375% ropivacaine. The secondary outcomes included cumulative oxycodone consumption, acute pain intensity, mechanical ventilation time, hospital length of stay, and postoperative complications. CPSP intensity was lower in the ESPB group than in the CON group 1, 3, and 6 months post-surgery (p < 0.001). Significant between-group differences were also observed in other outcomes, including postoperative pain severity, opioid consumption, mechanical ventilation time, and hospital length of stay, in favor of the ESPB group. Preemptive ESPB appears to decrease the risk of CPSP development in patients undergoing OP-CABG. Reduced acute pain severity and shorter mechanical ventilation times and hospital stays should improve patients’ satisfaction and reduce perioperative complications.