Endogenous thrombin potential following hemostatic therapy with 4-factor prothrombin complex concentrate: a 7-day observational study of trauma patients.

INTRODUCTION: Purified prothrombin complex concentrate (PCC) is increasingly used as hemostatic therapy for trauma-induced coagulopathy (TIC). However, the impact of PCC administration on coagulation status among patients with TIC has not been adequately investigated. METHODS: In this observational, descriptive study, data relating to thrombin generation were obtained from plasma samples gathered prospectively from trauma patients upon emergency room (ER) admission and over the following 7 days. Standard coagulation tests, including measurement of antithrombin (AT) and fibrinogen, were performed. Three groups were investigated: patients receiving no coagulation therapy (NCT group), patients receiving fibrinogen concentrate only (FC group), and patients treated with PCC and fibrinogen concentrate (FC-PCC group). RESULTS: The study population (77 patients) was predominantly male (84.4%); mean age was 40 ± 15 years and mean injury severity score was 25.6 ± 12.7. There were no significant differences between the three study groups in thrombin-related parameters upon ER admission. Endogenous thrombin potential (ETP) was significantly higher in the FC-PCC group compared with the NCT group on days 1 to 4 and the FC group on days 1 to 3. AT levels were significantly lower in the FC-PCC group from admission until day 3 (versus FC group) or day 4 (versus NCT group). Fibrinogen increased over time, with no significant between-group differences after ER admission. Despite ETP being higher, prothrombin time and activated partial thromboplastin time were significantly prolonged in the FC-PCC group from admission until day 3 to 4. CONCLUSIONS: Treatment with PCC increased ETP for several days, and patients receiving PCC therapy had low AT concentrations. These findings imply a potential pro-thrombotic state not reflected by standard coagulation tests. This is probably important given the postoperative acute phase increase in fibrinogen levels, although studies with clinical endpoints are needed to ascertain the implications for patient outcomes. We recommend careful use of PCC among trauma patients, with monitoring and potentially supplementation of AT.

Peripheral Regional Anesthesia Using Local Anesthetics: Old Wine in New Bottles?

During the past decade, numerous efforts were undertaken aiming at prolonging the analgesic effect of regional anesthesia. With the development of extended-release formulations and enhanced selectivity for nociceptive sensory neurons, a very promising contribution to the development of pain medications has been achieved. At present, liposomal bupivacaine is the most popular, non-opioid, controlled drug delivery system, but its duration of action, which is still controversially discussed, and its expensiveness have decreased initial enthusiasm. Continuous techniques can be seen as an elegant alternative for providing a prolonged duration of analgesia, but for logistic or anatomical reasons, they are not always the best choice. Therefore, focus has been directed towards the perineural and/or intravenous addition of old and established substances. As for perineural application, most of these so-called 'adjuvants' are used outside their indication, and their pharmacological efficacy is often not or only poorly understood. This review aims to summarize the recent developments for prolonging the duration of regional anesthesia. It will also discuss the potential harmful interactions and side effects of frequently used analgesic mixtures.

Incidence, risk factors and outcome of acute kidney injury in critically ill COVID-19 patients in Tyrol, Austria: a prospective multicenter registry study.

INTRODUCTION: Acute kidney injury is a frequent complication in critically ill patients with and without COVID-19. The aim of this study was to evaluate the incidence of, and risk factors for, acute kidney injury and its effect on clinical outcomes of critically ill COVID-19 patients in Tyrol, Austria. METHODS: This multicenter prospective registry study included adult patients with a SARS-CoV-2 infection confirmed by polymerase chain reaction, who were treated in one of the 12 dedicated intensive care units during the COVID-19 pandemic from February 2020 until May 2022. RESULTS: In total, 1042 patients were included during the study period. The median age of the overall cohort was 66 years. Of the included patients, 267 (26%) developed acute kidney injury during their intensive care unit stay. In total, 12.3% (n = 126) required renal replacement therapy with a median duration of 9 (IQR 3-18) days. In patients with acute kidney injury the rate of invasive mechanical ventilation was significantly higher with 85% (n = 227) compared to 41% (n = 312) in the no acute kidney injury group (p < 0.001). The most important risk factors for acute kidney injury were invasive mechanical ventilation (OR = 4.19, p < 0.001), vasopressor use (OR = 3.17, p < 0.001) and chronic kidney disease (OR = 2.30, p < 0.001) in a multivariable logistic regression analysis. Hospital and intensive care unit mortality were significantly higher in patients with acute kidney injury compared to patients without acute kidney injury (Hospital mortality: 52.1% vs. 17.2%, p < 0.001, ICU-mortality: 47.2% vs. 14.7%, p < 0.001). CONCLUSION: As in non-COVID-19 patients, acute kidney injury is clearly associated with increased mortality in critically ill COVID-19 patients. Among known risk factors, invasive mechanical ventilation has been identified as an independent and strong predictor of acute kidney injury.

Changes in characteristics and outcomes of critically ill COVID-19 patients in Tyrol (Austria) over 1 year.

BACKGROUND: Widely varying mortality rates of critically ill Coronavirus disease 19 (COVID-19) patients in the world highlighted the need for local surveillance of baseline characteristics, treatment strategies and outcome. We compared two periods of the COVID-19 pandemic to identify important differences in characteristics and therapeutic measures and their influence on the outcome of critically ill COVID-19 patients. METHODS: This multicenter prospective register study included all patients with a SARS-CoV­2 infection confirmed by polymerase chain reaction, who were treated in 1 of the 12 intensive care units (ICU) from 8 hospitals in Tyrol, Austria during 2 defined periods (1 February 2020 until 17 July: first wave and 18 July 2020 until 22 February 2021: second wave) of the COVID-19 pandemic. RESULTS: Overall, 508 patients were analyzed. The majority (n = 401) presented during the second wave, where the median age was significantly higher (64 years, IQR 54-74 years vs. 72 years, IQR 62-78 years, p < 0.001). Invasive mechanical ventilation was less frequent during the second period (50.5% vs 67.3%, p = 0.003), as was the use of vasopressors (50.3% vs. 69.2%, p = 0.001) and renal replacement therapy (12.0% vs. 19.6%, p = 0.061), which resulted in shorter ICU length of stay (10 days, IQR 5-18 days vs. 18 days, IQR 5-31 days, p < 0.001). Nonetheless, ICU mortality did not change (28.9% vs. 21.5%, p = 0.159) and hospital mortality even increased (22.4% vs. 33.4%, p = 0.039) in the second period. Age, frailty and the number of comorbidities were significant predictors of hospital mortality in a multivariate logistic regression analysis of the overall cohort. CONCLUSION: Advanced treatment strategies and learning effects over time resulted in reduced rates of mechanical ventilation and vasopressor use in the second wave associated with shorter ICU length of stay. Despite these improvements, age appears to be a dominant factor for hospital mortality in critically ill COVID-19 patients.

Structured ICU resource management in a pandemic is associated with favorable outcome in critically ill COVID­19 patients.

INTRODUCTION: On February 25, 2020, the first 2 patients were tested positive for severe acute respiratory syndrome coronavirus­2 (SARS-CoV-2) in Tyrol, Austria. Rapid measures were taken to ensure adequate intensive care unit (ICU) preparedness for a surge of critically ill coronavirus disease-2019 (COVID-19) patients. METHODS: This cohort study included all COVID-19 patients admitted to an ICU with confirmed or strongly suspected COVID-19 in the State of Tyrol, Austria. Patients were recorded in the Tyrolean COVID-19 intensive care registry. Date of final follow-up was July 17, 2020. RESULTS: A total of 106 critically ill patients with COVID-19 were admitted to 1 of 13 ICUs in Tyrol from March 9 to July 17, 2020. Median age was 64 years (interquartile range, IQR 54-74 years) and the majority of patients were male (76 patients, 71.7%). Median simplified acute physiology score III (SAPS III) was 56 points (IQR 49-64 points). The median duration from appearance of first symptoms to ICU admission was 8 days (IQR 5-11 days). Invasive mechanical ventilation was required in 72 patients (67.9%) and 6 patients (5.6%) required extracorporeal membrane oxygenation treatment. Renal replacement therapy was necessary in 21 patients (19.8%). Median ICU length of stay (LOS) was 18 days (IQR 5-31 days), median hospital LOS was 27 days (IQR 13-49 days). The ICU mortality was 21.7% (23 patients), hospital mortality was 22.6%. There was no significant difference in ICU mortality in patients receiving invasive mechanical ventilation and in those not receiving it (18.1% vs. 29.4%, p = 0.284). As of July 17th, 2020, two patients are still hospitalized, one in an ICU, one on a general ward. CONCLUSION: Critically ill COVID-19 patients in Tyrol showed high severity of disease often requiring complex treatment with increased lengths of ICU and hospital stay. Nevertheless, the mortality was found to be remarkably low, which may be attributed to our adaptive surge response providing sufficient ICU resources.

Unilateral anesthesia does not affect the incidence of urinary retention after low-dose spinal anesthesia for knee surgery.

We evaluated whether unilateral low-dose spinal anesthesia may reduce the likelihood of postoperative urinary retention. Forty patients scheduled for knee arthroscopy randomly received bilateral (n = 20) or unilateral (n = 20) spinal anesthesia with 6-mg hyperbaric bupivacaine 0.5%. The incidence of urinary retention (>500 mL) assessed with an ultrasound device (Bladderscan) and subsequent temporary catherization was 7/20 patients in the bilateral versus 6/20 in the unilateral group (not significant). We concluded that unilateral low-dose spinal anesthesia does not further decrease the likelihood of urinary retention. Our results demonstrate the value and necessity of monitoring bladder volume postoperatively.

Lumbar plexus and psoas major muscle: not always as expected.

BACKGROUND AND OBJECTIVES: Conflicting definitions concerning the exact location of the lumbar plexus have been proposed. The present study was carried out to detect anatomical variants regarding the topographical relation between the lumbar plexus and the psoas major muscle as well as lumbar plexus anatomy at the L4-L5 level. METHODS: Sixty-three lumbar plexuses from 32 embalmed cadavers were dissected to determine the topographical relation between lumbar plexus and psoas major muscle. At the L4-L5 levels variability in the course of the femoral as well as obturator nerve were described. RESULTS: The lumbar plexus was situated within the psoas major muscle in 61 of 63 cases. In 2 of 63 cases the entire plexus was localized posterior to the psoas major muscle. In the 61 of 63 cases in which the lumbar plexus was situated within the psoas major muscle, emergence of the individual nerves most often occurred on the posterior or posterolateral surface. CONCLUSIONS: Our results synthesize contrasting assumptions in previous literature, by demonstrating that both locations of the lumbar plexus may be encountered in clinical practice: within and posterior to the psoas major muscle. However, the latter situation represents a minor variant. At the level of L4-L5 the femoral nerve, showing a remarkable degree of branching, as well as the obturator nerve, were found within the psoas major muscle in the vast majority of specimens.

In vitro, lidocaine-induced axonal injury is prevented by peripheral inhibition of the p38 mitogen-activated protein kinase, but not by inhibiting caspase activity.

BACKGROUND: All local anesthetics (LAs) are, to some extent, neurotoxic. Toxicity studies have been performed in dissociated neuron cultures, immersing both axon and soma in LA. This approach, however, does not accurately reflect the in vivo situation for peripheral nerve blockade, where LA is applied to the axon alone. METHODS: We investigated lidocaine neurotoxicity in compartmental sensory neuron cultures, which are composed of one central compartment containing neuronal cell bodies and a peripheral compartment containing their axons, allowing for selective incubation. We applied lidocaine +/- neuroprotective drugs to neuronal somata or axons, and assessed neuron survival and axonal outgrowth. RESULTS: Lidocaine applied to the peripheral compartment led to a decreased number of axons (to 59% +/- 9%), without affecting survival of cell bodies. During axonal incubation with lidocaine, the p38 mitogen-activated protein kinase inhibitor SB203580 (10 microM) attenuated axonal injury when applied to the axon (insignificant reduction of maximal axonal distance to 93% +/- 9%), but not when applied to the cell body (deterioration of maximal axonal length to 48% +/- 6%). Axonal co-incubation of lidocaine with the caspase inhibitor z-vad-fmk (20 microM) was not protective. CONCLUSIONS: Whereas inhibition of either p38 mitogen-activated protein kinase or caspase activity promote neuronal survival after LA treatment of dissociated neuronal cultures, axonal degeneration induced by lidocain (40 mM) is prevented by p38 MAP kinase but not by caspase inhibition. We conclude that processes leading to LA-induced neurotoxicity in dissociated neuronal culture may be different from those observed after purely axonal application.

Ultrasound guidance for the psoas compartment block: an imaging study.

UNLABELLED: We conducted this study to develop an ultrasound-guided approach to the psoas compartment and to assess its feasibility and accuracy by means of computed tomography (CT). Two examiners performed ultrasound-guided approaches at three levels (L2-3, L3-4, and L4-5) on 10 embalmed cadavers, which were seated prone. After each needle had been advanced into the psoas compartment under ultrasound guidance, the positions of their tips were computed by using two coordinates (A and B). Subsequently, axial transverse CT scans were made to verify the ultrasound measurements by using the same coordinates. In total, 48 approaches were performed (Examiner 1, n = 20; Examiner 2, n = 28). CT revealed that 47 of 48 ultrasound-guided approaches were performed exactly. In 1 of 48 approaches (L3-4), the tip of the needle was located posterior to the psoas muscle. The median differences between ultrasound and CT coordinates were 0.3 plus minus 0.3 cm for A and 0.2 plus minus 0.3 for B. Kendall's coefficient of concordance was 0.9 (P < 0.001) between ultrasound and CT measurements for both coordinates. These results indicate that ultrasound enables exact needle placement, as proved by CT. We conclude that ultrasound guidance might be a useful adjunct to increase the safety and efficacy of the psoas compartment block at these levels. IMPLICATIONS: We developed an ultrasound-guided approach to the psoas compartment at the levels L2-3, L3-4, and L4-5. Feasibility and accuracy were tested on embalmed cadavers and verified by means of computed tomography. Ultrasound guidance proved to be feasible and accurate for the performance of psoas compartment blocks.

The incidence of lumbar ligamentum flavum midline gaps.

UNLABELLED: Lumbar epidural anesthesia and analgesia has gained increasing importance in perioperative pain therapy for abdominal and lower limb surgery. The loss-of-resistance technique, used to identify the epidural space, is thought to rely on the penetration of the ligamentum flavum. However, the exact morphology of the ligamentum flavum at different vertebral levels remains controversial. Therefore, in this study, we directly investigated the incidence of lumbar ligamentum flavum midline gaps in embalmed cadavers. Vertebral column specimens were obtained from 45 human cadavers. On each dissected level, ligamentum flavum midline gaps were recorded. The incidence of midline gaps per number of viable specimens at the following levels was: L1-2 = 10 of 45 (22.2%), L2-3 = 5 of 44 (11.4%), L3-4 = 5 of 45 (11.1%), L4-5 = 4 of 43 (9.3%), L5/S1 = 0 of 33 (0%). In conclusion, the present study determined the frequency of lumbar ligamentum flavum midline gaps. Gaps in the lumbar ligamentum flavum are most frequent between L1 and L2 but are more rare below this level. When using the midline approach, the ligamentum flavum may not impede entering the epidural space in all patients. IMPLICATIONS: The ligamentum flavum is a crucial anatomical landmark for the safe performance of epidural anesthesia. However, the present study demonstrates some failure of the lumbar ligamentum flavum as a landmark. This may mean that, using a midline approach, one cannot always rely on the ligamentum flavum as a perceptible barrier to epidural needle advancement.

Ultrasound-guided lumbar facet nerve block: accuracy of a new technique confirmed by computed tomography.

BACKGROUND: Lumbar facet nerve (medial branch) blocks are often used to diagnose facet joint-mediated pain. The authors recently described a new ultrasound-guided methodology. The current study determines its accuracy using computed tomography scan controls. METHODS: Fifty bilateral ultrasound-guided approaches to the lumbar facet nerves were performed in five embalmed cadavers. The target point was the groove at the cephalad margin of the transverse (or costal) process L1-L5 (medial branch T12-L4) adjacent to the superior articular process. Axial transverse computed tomography scans, with and without 1 ml contrast dye, followed to evaluate needle positions and spread of contrast medium. RESULTS: Forty-five of 50 needle tips were located at the exact target point. The remaining 5 were within 5 mm of the target. In 47 of 50 cases, the applied contrast dye reached the groove where the nerve is located, corresponding to a simulated block success rate of 94% (95% confidence interval, 84-98%). Seven of 50 cases showed paraforaminal spread, 5 of 50 showed epidural spread, and 2 of 50 showed intravascular spread. Despite the aberrant distribution, all of these approaches were successful, as indicated by contrast dye at the target point. Abnormal contrast spread was equally distributed among all lumbar levels. Contrast traces along the needle channels were frequently observed. CONCLUSIONS: : The computed tomography scans confirm that our ultrasound technique for lumbar facet nerve block is highly accurate for the target at all five lumbar transverse processes (medial branches T12-L4). Aberrant contrast medium spread is comparable to that of the classic fluoroscopy-guided method.

Ultrasound-guided lumbar facet nerve block: a sonoanatomic study of a new methodologic approach.

BACKGROUND: Lumbar facet nerve (medial branch) block for pain relief in facet syndrome is currently performed under fluoroscopic or computed tomography scan guidance. In this three-part study, the authors developed a new ultrasound-guided methodology, described the necessary landmarks and views, assessed ultrasound-derived distances, and tested the clinical feasibility. METHODS: (1) A paravertebral cross-axis view and long-axis view were defined under high-resolution ultrasound (15 MHz). Three needles were guided to the target point at L3-L5 in a fresh, nonembalmed cadaver under ultrasound (2-6 MHz) and were subsequently traced by means of dissection. (2) The lumbar regions of 20 volunteers (9 women, 11 men; median age, 36 yr [23-67 yr]; median body mass index, 23 kg/m2 [19-36 kg/m2]) were studied with ultrasound (3.5 MHz) to assess visibility of landmarks and relevant distances at L3-L5 in a total of 240 views. (3) Twenty-eight ultrasound-guided blocks were performed in five patients (two women, three men; median age, 51 yr [31-68 yr]) and controlled under fluoroscopy. RESULTS: In the cadaver, needle positions were correct as revealed by dissection at all three levels. In the volunteers, ultrasound landmarks were delineated as good in 19 and of sufficient quality in one (body mass index, 36 kg/m2). Skin-target distances increased from L3 to L5, reaching statistical significance (*, **P < 0.05) between these levels on both sides: L3r, 45+/-6 mm*; L4r, 48+/-7 mm; L5r, 50+/-6 mm*; L3l, 44+/-5 mm**; L4l, 47+/-6 mm; L5l, 50+/-6 mm**. In patients, 25 of 28 ultrasound-guided needles were placed accurately, with the remaining three closer than 5 mm to the radiologically defined target point. CONCLUSION: Ultrasound guidance seems to be a promising new technique with clinical relevance and the potential to increase practicability while avoiding radiation in lumbar facet nerve block.

Lumbar plexus in children. A sonographic study and its relevance to pediatric regional anesthesia.

BACKGROUND: Pediatric regional anesthesia has gained increasing interest over the past decades. The current study was conducted to investigate the lumbar paravertebral region and the lumbar plexus at L3-L4 and L4-L5 by means of sonography to obtain fundamentals for the performance of ultrasound-guided posterior lumbar plexus blocks. METHODS: Thirty-two children (12 boys, 20 girls) with American Society of Anesthesiologists physical status I or II were enrolled in the current study. The lumbar paravertebral region was visualized at L3-L4 and L4-L5 on two corresponding posterior sonograms (longitudinal, transverse). The lumbar plexus had to be delineated, and skin-plexus distances were measured. In a series of five pediatric patients undergoing inguinal herniotomy, ultrasound-guided posterior lumbar plexus blocks at L4-L5 were performed. RESULTS: The children were stratified into three age groups (group 1: > 3 yr and 5 yr and 8 yr and

Cervical and high thoracic ligamentum flavum frequently fails to fuse in the midline.

BACKGROUND: Cervical and high thoracic epidural anesthesia and analgesia have gained increasing importance in the treatment of painful conditions and as components of anesthetics for cardiac and breast surgery. In contrast to the hanging-drop technique, the loss-of-resistance technique is thought to rely on the penetration of the ligamentum flavum. However, the exact morphology of the ligamentum flavum at different vertebral levels remains controversial. Therefore, the aim of this study was to investigate the incidence and morphology of cervical and high thoracic ligamentum flavum mid-line gaps in embalmed cadavers. METHODS: Vertebral column specimens were obtained from 52 human cadavers. On each dissected level, ligamentum flavum mid-line gaps were recorded and evaluated with respect to shape and size. RESULTS: The following variations were encountered: complete fusion in the mid-line, mid-line fusion with a gap in the caudal part, mid-line gap, and mid-line gap with widened caudal end. The incidence of mid-line gaps at the following levels was: C3-C4: 66%, C4-C5: 58%, C5-C6: 74%, C6-C7: 64%, C7-T1: 51%, Th1-Th2: 21%, Th2-Th3: 11%, Th3-Th4: 4%, Th4-Th5: 2%, and Th5-Th6: 2%. The mean width of mid-line gaps was 1.0 +/- 0.3 mm. CONCLUSIONS: In conclusion, the present study shows that gaps in the ligamenta flava are frequent at cervical and high thoracic levels but become rare at the T3/T4 level and below, such that one cannot always rely on the ligamentum flavum as a perceptible barrier to epidural needle placement at these levels.