Triggering receptor expressed on myeloid cells-1 in sepsis, and current insights into clinical studies.

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a pattern recognition receptor and plays a critical role in the immune response. TREM-1 activation leads to the production and release of proinflammatory cytokines, chemokines, as well as its own expression and circulating levels of the cleaved soluble extracellular portion of TREM-1 (sTREM-1). Because patients with sepsis and septic shock show elevated sTREM-1 levels, TREM-1 has attracted attention as an important contributor to the inadequate immune response in this often-deadly condition. Since 2001, when the first blockade of TREM-1 in sepsis was performed, many potential TREM-1 inhibitors have been established in animal models. However, only one of them, nangibotide, has entered clinical trials, which have yielded promising data for future treatment of sepsis, septic shock, and other inflammatory disease such as COVID-19. This review discusses the TREM-1 pathway and important ligands, and highlights the development of novel inhibitors as well as their clinical potential for targeted treatment of various inflammatory conditions.

Notch Signaling in Acute Inflammation and Sepsis.

Notch signaling, a highly conserved pathway in mammals, is crucial for differentiation and homeostasis of immune cells. Besides, this pathway is also directly involved in the transmission of immune signals. Notch signaling per se does not have a clear pro- or anti-inflammatory effect, but rather its impact is highly dependent on the immune cell type and the cellular environment, modulating several inflammatory conditions including sepsis, and therefore significantly impacts the course of disease. In this review, we will discuss the contribution of Notch signaling on the clinical picture of systemic inflammatory diseases, especially sepsis. Specifically, we will review its role during immune cell development and its contribution to the modulation of organ-specific immune responses. Finally, we will evaluate to what extent manipulation of the Notch signaling pathway could be a future therapeutic strategy.

[Intranasal lidocaine atomization as novel and noninvasive treatment option for postdural puncture headache : Two case reports from obstetric anesthesiology]. / Intranasale Lidocainvernebelung als neue und nichtinvasive Therapieoption des Postpunktionskopfschmerzes : Zwei Fallberichte aus der geburtshilflichen Anästhesiologie.

BACKGROUND: Postdural puncture headache (PDPH) occurs in up to 11% of patients after spinal anesthesia and in more than 80% after dural perforation upon epidural anesthesia. It represents a severe anesthesiological complication in obstetric patients. If conservative medication measures do not result in a timely relief of symptoms, the current guidelines recommend the early implementation of an epidural blood patch; however, although performing an epidural blood patch is effective to treat PDPH, potential side effects include neurological complications, spinal hematoma and infections. Assumed to reduce cerebral vasodilatation as a potential pathophysiological driver of PDPH, the transnasal block of the sphenopalatine ganglion with local anesthetics is discussed as an alternative approach. METHODS: In this case study a modification of this technique is reported using a mucosal atomization device (MAD) for off-label nasal administration of lidocaine in two obstetric patients suffering from PDPH. Up to now there is no experience with this modified technique in obstetric anesthesiology. RESULTS: The first patient (25-year-old secundigravida, body mass index [BMI] 54.7 kg/m2) displayed a pronounced PDPH with nausea and vomiting during the first day after a cesarean section under spinal anesthesia (3 attempts). The second patient (32-year-old tertiagravida, BMI 27.3 kg/m2) was readmitted to hospital due to PDPH 4 days after a natural birth under epidural anesthesia. Whereas conservative measures and therapeutic attempts with nonopioid analgesics and caffeine did not result in a sufficient treatment success, intranasal lidocaine administration via a MAD led to an immediate and persisting symptom relief. Both patients could be discharged from hospital after 24 h of surveillance and did not report any relevant side effects of the lidocaine administration. CONCLUSION: The described noninvasive and simple procedure represents a valuable addition to previously known treatment options for PDPH and a potential alternative to an epidural blood patch in obstetric patients with PDPH. Prospective studies are needed to validate the findings.

Sepsis in mechanically ventilated patients with spinal cord injury: a retrospective analysis.

STUDY DESIGN: Retrospective analysis. OBJECTIVES: Sepsis, one of the most frequent and life-threatening complications on intensive care units (ICUs), is associated with a need for mechanical ventilation (MV) as well as adverse respiratory outcomes in hospitalized individuals. However, it has poorly been investigated in patients with spinal cord injury (SCI); a population at high risk for pulmonary and infectious complications. SETTING: Spinal Cord Injury Center, Heidelberg University Hospital. METHODS: Over a 5-year period, 182 individuals with SCI requiring MV during their ICU stay were analyzed. Data assessment included demographics, medical characteristics, focus and causative pathogen of sepsis, length of stay, weaning outcomes, and mortality. RESULTS: Sepsis was recorded in 28 patients (15%), containing a subgroup of individuals suffering from infectious SCI and co-occurring primary sepsis with Staphylococcus aureus as the predominant microorganism. In most individuals, sepsis was found as secondary complication, which was associated with pulmonary foci, Gram-negative bacteria, and high mortality. More than 80% of individuals with secondary sepsis required induction of MV due to respiratory failure. Furthermore, respiratory failure was found to be independent of sepsis focus, spectrum of causative pathogens, SCI etiology, or severity of injury. Subsequent weaning from the respirator was prolonged in more than 90% with a high proportion of weaning failure. CONCLUSIONS: Sepsis predominantly occurs as a secondary complication after SCI and is associated with detrimental outcomes. Although the lung is frequently affected as a failing organ, not all sepsis foci are pulmonary. Awareness of both actual sepsis focus and causative pathogen is central to initiate an adequate sepsis treatment.

Prolonged antibiotic prophylaxis after thoracoabdominal esophagectomy does not reduce the risk of pneumonia in the first 30 days: a retrospective before-and-after analysis.

PURPOSE: Thoracoabdominal esophageal resection for malignant disease is frequently associated with pulmonary infection. Whether prolonged antibiotic prophylaxis beyond a single perioperative dose is advantageous in preventing pulmonary infection after thoracoabdominal esophagectomy remains unclear. METHODS: In this retrospective before-and-after analysis, 173 patients between January 2009 and December 2014 from a prospectively maintained database were included. We evaluated the effect of a 5-day postoperative course of moxifloxacin, which is a frequently used antimicrobial agent for pneumonia, on the incidence of pulmonary infection and mortality after thoracoabdominal esophagectomy. RESULTS: 104 patients received only perioperative antimicrobial prophylaxis (control group) and 69 additionally received a 5-day postoperative antibiotic therapy with moxifloxacin (prolonged-course). 22 (12.7%) of all patients developed pneumonia within the first 30 days after surgery. No statistically significant differences were seen between the prolonged group and control group in terms of pneumonia after 7 (p = 0.169) or 30 days (p = 0.133), detected bacterial species (all p > 0.291) and 30-day mortality (5.8 vs 10.6%, p = 0.274). CONCLUSION: A preemptive 5-day postoperative course of moxifloxacin does not reduce the incidence of pulmonary infection and does not improve mortality after thoracoabdominal esophagectomy.

Inflammation and Its Consequences After Surgical Versus Transcatheter Aortic Valve Replacement.

Symptomatic aortic stenosis can be treated by surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR), the latter of which is regarded as a minimally invasive procedure. Differences between these procedures regarding immune responses or changes in coagulation and neurocognitive function have thus far been evaluated only sparsely. We carried out a prospective, single-center, nonrandomized explorative study with 38 patients. Thirteen patients were subjected to either SAVR or transfemoral (TF-) TAVR, and 12 patients underwent transapical (TA-) TAVR. Plasma cytokines (IL-6, -8, -18, presepsin) and acute-phase proteins (C-reactive protein, procalcitonin), markers of coagulation and platelet function, and neurocognitive function (via various standard tests) were assessed before and at five-time points during a 72-h follow-up after surgery. SAVR and TA-TAVR patients responded similarly to the procedure in terms of C-reactive protein, leukocyte numbers, and IL-6, whereas these responses were substantially lower in TF-TAVR patients. Only SAVR patients showed measurable IL-10 levels. SAVR patients without prior anticoagulation experienced a robust and transient restoration of platelet function after surgery, with no hypercoagulation observable in functional coagulation assays. None of the procedures led to an immediate improvement of hand and leg coordination, but patients after TA-TAVR had decreased neurocognitive function. Patients after SAVR or TA-TAVR exhibit a robust pro-inflammatory response, which is-on the cytokine level-counterbalanced only in SAVR patients. Our results point toward a greater impact of TA-TAVR on neurocognitive function and indicate a potentially detrimental activation of platelets in some patients after SAVR.

Risk factors for early viral infections after liver transplantation.

PURPOSE: Viral infections represent a serious threat for patients after liver transplantation (LT). The identification of risk factors during the early post-transplant period might help to improve prevention of viral infections after LT. METHODS: Between 2004 and 2010, 530 adult patients underwent LT at a large university hospital serving a metropolitan region in Europe. This retrospective single-centre study analysed putative risk factors for early viral infections with herpes simplex virus-1 (HSV-1), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), hepatitis A/B/C (HAV/HBV/HCV) and cytomegalovirus (CMV) in the first 3 months after LT. RESULTS: The final analysis included 501 patients of whom 126 (25.1%) had documented viral infections after LT. No significant differences could be detected between patients with or without viral infections concerning 30- and 90-day mortality. Risk factors in the early post-transplant period identified by multivariate analysis included female gender (CMV, HSV-1), the post-operative need for continuous veno-venous hemofiltration (CMV), septic shock (CMV), detection of fungi (CMV) and the intraoperative amount of transfused blood (EBV). CONCLUSIONS: Enhanced vigilance regarding opportunistic infections is crucial in the management of this high-risk population of immunocompromised patients. In particular, attention should be paid to avoidable conditions that increase the risk of renal replacement therapies in the post-LT setting, especially among women. TRIAL REGISTRATION: DRKS00010672 on German Clinical Trial Register.

Advanced glycation endproducts induce self- and cross-tolerance in monocytes.

INTRODUCTION: Advanced glycation endproducts (AGEs) are well-known inflammatory mediators, which are recognized by immune cells through their corresponding receptor RAGE and have been shown to participate in the pathophysiology of a variety of acute as well as chronic inflammatory diseases. Nevertheless, no data are available on the aftermath of AGE recognition on immune cells. MATERIALS AND METHODS: We used the monocytic cell line MonoMac6 as well as primary human monocytes for double stimulation experiments. We measured secreted as well as intracellular levels of TNF-α using ELISA and flow cytometry. In addition, gene expression of surface receptors (RAGE and TLR4) and TNF were measured by qPCR. RESULTS: Stimulation with AGE leads to a dose-dependent induction of self- and cross-tolerance in both primary monocytes as well as the MonoMac6 cell line. The AGE tolerance depended neither on a decreased expression of RAGE or TLR4, nor on a decrease of TNF-α expression. Nevertheless, intracellular TNF-α was decreased, hinting towards a posttranscriptional regulation. CONCLUSION: High levels of AGEs are capable to activate immune cells at first, but induce a secondary state of hypo-responsiveness in these cells. Based on the origin of its causal agent, we propose this phenomenon to be "metabolic tolerance".

Plasma DNA and RNA differentially impact coagulation during abdominal sepsis-an explorative study.

BACKGROUND: Cell-free DNA (cfDNA) and extracellular RNA (exRNA) are both suspected to activate coagulation cascades in sepsis. Therefore, our study investigated the influence of plasmatic nucleic acids on coagulation in septic patients in comparison to patients after major abdominal surgery. MATERIALS AND METHODS: A total of 15 patients with sepsis, 10 postoperative patients, and 10 healthy volunteers were included in this longitudinal study. Blood was collected at sepsis onset and after surgery respectively, as well as after 24, 72 and 168 h. Levels of cfDNA and exRNA were measured by quantitative probe-based polymerase chain reaction. In addition, thromboelastography for coagulation as well as thromboaggregometry for platelet function was conducted. RESULTS: Both cfDNA and exRNA were elevated in patients with sepsis compared with postoperative patients and healthy volunteers. While higher exRNA levels correlated with a faster clotting time and more stable clots, cfDNA correlated with a shorter clotting time but also less fibrinolysis. In addition, higher cfDNA seems to be associated with kidney dysfunction as well as with general markers of cell damage (lactate dehydrogenase and lactate). CONCLUSIONS: Both nucleic acid species might be associated with different effects on coagulation during sepsis, with an overall procoagulatory influence. For this reason, individualized therapeutic approaches in patients suffering from coagulation-associated organ dysfunction might be feasible.

Anesthetic Management for Percutaneous Minimally Invasive Fetoscopic Surgery of Spina Bifida Aperta: A Retrospective, Descriptive Report of Clinical Experience.

Minimally invasive fetoscopic surgery for spina bifida aperta is a new therapeutic approach to preserve neurologic function by protecting exposed neural tissue. The anesthetic management is of paramount importance for the success of the procedure. Therefore, our protocol was developed with particular attention to safe and adequate maternal and fetal anesthesia, sufficient uterine relaxation as well as prevention of pulmonary edema, placental abruption, and spontaneous labor. As illustrated by this retrospective analysis of 61 cases, these goals can be reliably achieved. The clinical protocol is presented as a supplemental digital content to this manuscript (Supplemental Digital Content 1, http://links.lww.com/AA/B733).

Sepsis varies arterial two-pore-domain potassium channel messenger RNA in mice.

BACKGROUND: Hemodynamic changes are mainly responsible for organ failure and subsequently for the poor outcome of sepsis. Occurring macro- and micro-circulatory dysfunctions are not homogeneously distributed in the vessel beds. Especially mesenteric arterioles are subject to hypoperfusion during sepsis, and in consequence, a dysfunction of the downstream organs develops. Furthermore, impaired perfusion of the splanchnic area may cause intestinal barrier breakdown supporting the translocation of bacteria or toxins into the circulation aggravating a systemic infection and organ failure. The two-pore potassium channels (K2P channels) are responsible for setting the resting membrane potential of smooth muscle cells. Because of their sensitivity by various metabolic or humoral mediators, which are also varying during inflammatory processes, they can determine vascular resistance during sepsis. Dopamine receptors type 1 (D1R) and 2 (D2R) are assumed to be involved in the regulation of arterial tone under hypoxic conditions and are investigated too. MATERIALS AND METHODS: Sepsis was induced in mice by the cecal ligation and puncture model. This study investigates the expression of K2P channels and the dopamine receptors at RNA level by real-time polymerase chain reaction analysis and two K2P channels at the protein level by Western blotting. RESULTS: The RNA levels of K2P channels respond differently to sepsis. Although the weakly inward rectifying K+ channel 2 (TWIK 2) is not affected, TWIK-related acid-sensitive K+ channel 1 and 2 (TASK 1 and TASK 2) and TWIK-related K+ channel 1 (TREK 1) are partially downregulated during the course of the experiment. A downregulation of D1R and an upregulation of the D2R could be observed during the septic phase. CONCLUSIONS: The changes shown could be important factors for the reduced mesenteric perfusion during sepsis.

Role of the RAGE Axis during the Immune Response after Severe Trauma: A Prospective Pilot Study.

BACKGROUND: Severe traumatization induces a complex pathophysiology, driven by the patient's own immune system. The initial activation is a result of damage-associated molecular patterns, which are released from disrupted and dying cells and recognized by immune receptors, for example, RAGE. In this study we aimed to evaluate the contribution of the RAGE axis to early and late immune responses. METHODS: We enrolled 16 patients with severe trauma together with 10 patients after major abdominal surgery and 10 healthy volunteers. Blood samples were taken on admission and every 48 h for a total of 8 days. Plasma concentrations of various RAGE ligands as well as RAGE isoforms and IL-6 were measured by ELISA. Monocyte surface expression of RAGE and HLA-DR was assessed by flow cytometry. RESULTS: High and transient levels of IL-6 and methylglyoxal characterize the early immune response after trauma, whereas samples from later time points provide evidence for a secondary release of RAGE ligands. CONCLUSION: Our results provide evidence for a persisting activation of the RAGE axis while classical mediators like IL-6 disappear early. Considering the immunocompromised phenotype of the monocytes, the RAGE ligands might be substantial contributors to the well-known secondary stage of impaired immune responsiveness in trauma patients.

Incomplete sensorimotor paresis after upper abdominal surgery with TEA and spinal epidural lipomatosis: a case report.

INTRODUCTION: This case report documents a postoperative, incomplete sensorimotor paraparesis from thoracic vertebral body 6 (Th6) after combined anesthesia for upper abdominal surgery in a patient who had a thoracic localization of spinal epidural lipomatosis (SEL). CASE PRESENTATION: The patient was treated in our clinic with a thoracic epidural catheter (TEA) for perioperative analgesia during a partial duodenopancreatectomy. Paraparetic symptoms occurred 20 hours after surgery. Initial MRI did not show bleeding, infection or spinal cord damage and the neurosurgeon consultants recommended observation. The neurological examination and the third follow-up MRI on 15th postoperative day showed ventrolateral damage of the spinal cord at level Th6. It is possible that local anesthetic compressed the spinal cord in addition to the existing lipomatosis and the thoracic kyphosis. The paraparesis improved during follow-up paraplegiologic treatment. CONCLUSION: So far, only two uncomplicated lumbar epidural catheter anesthesias have been described in patients who had a lumbar SEL. Epidural catheter anesthesia is a safe and effective method of pain control. But it is important to carefully identify and stratify patients with risk factors during the premedication visit. In patients who had kyphosis and thoracic localization of SEL, TEA may only be used after a risk-benefit assessment.

Pulmonary Events in ICU patients with hyperoxia: is it possible to relate arterial partial pressure of oxygen to coded diseases? A retrospective analysis.

OBJECTIVE: Oxygen has been used liberally in ICUs for a long time to prevent hypoxia in ICU- patients. Current evidence suggests that paO2 >300 mmHg should be avoided, it remains uncertain whether an "optimal level" exists. We investigated how "mild" hyperoxia influences diseases and in-hospital mortality. DESIGN: This is a retrospective study. SETTING: 112 mechanically ventilated ICU-patients were enrolled. PATIENTS OR PARTICIPANTS: 112 ventilated patients were included and categorized into two groups based on the median paO2 values measured in initial 24 h of mechanical ventilation: normoxia group (paO2 ≤ 100 mmHg, n = 43) and hyperoxia group patients (paO2 > 100 mmHg, n = 69). INTERVENTIONS: No interventions were performed. MAIN VARIABLES OF INTEREST: The primary outcome was the incidence of pulmonary events, the secondary outcomes included the incidence of other new organ dysfunctions and in-hospital mortality. RESULTS: The baseline characteristics, such as age, body mass index, lactate levels, and severity of disease scores, were similar in both groups. There were no statistically significant differences in the incidence of pulmonary events, infections, and new organ dysfunctions between the groups. 27 out of 69 patients (39.1%) in the "mild" hyperoxia group and 12 out of 43 patients (27.9%) in the normoxia group died during their ICU or hospital stay (p = 0.54). The mean APACHE Score was 29.4 (SD 7.9) in the normoxia group and 30.0 (SD 6.7) in the hyperoxia group (p = 0.62). CONCLUSIONS: We found no differences in pulmonary events, other coded diseases, and in-hospital mortality between both groups. It remains still unclear what the "best oxygen regime" is for intensive care patients.

Impact of supplemental anesthesia in preterm infants undergoing inguinal hernia repair under spinal anesthesia : A retrospective analysis.

BACKGROUND: In preterm infants, spinal anesthesia (SpA) is recognized as an alternative to general anesthesia for inguinal hernia repair (IHR); however, some patients require supplemental anesthesia during surgery. The purpose of this study was to investigate the frequency and impact of supplemental anesthesia on perioperative care and adverse respiratory and hemodynamic events. METHODS: A retrospective study of preterm infants undergoing IHR at Heidelberg University Hospital within the first year of life between 2009 and 2018 was carried out. RESULTS: In total, 230 patients (255 surgeries) were investigated. Among 189 procedures completed using SpA 24 patients received supplemental anesthesia. Reasons for supplemental anesthesia included loss of anesthetic effect, returning motor response, and respiratory complications. Compared to SpA alone, no differences were found concerning hemodynamic parameters; however, patients requiring supplemental anesthesia displayed higher rates of postoperative oxygen supplementation and unexpected admission to the intensive care unit. The rate of perioperative apnea was 2.7%. Apneic events exclusively occurred after supplemental anesthesia. Bilateral IHR and duration of surgery were associated with the need for supplemental anesthesia. CONCLUSION: Whereas SpA might be favorable when compared to general anesthesia for IHR, the data indicate that particular caution is required in patients receiving supplemental anesthesia due to the possible risk for adverse respiratory events.

Abdominal surgery induces long-lasting changes in expression and binding of CTCF with impact on Major Histocompatibility Complex II transcription in circulating human monocytes.

BACKGROUND: Postoperative immunosuppression has been recognized as an important driver of surgery-related morbidity and mortality. It is characterized by lymphocyte depression and impaired monocyte capability to present foreign antigens to T-cells via Major Histocompatibility Complex, Class II (MHC-II) molecules. In patients with postoperative abdominal sepsis, we previously detected a persisting differential binding of the CCCTC-Binding Factor (CTCF), a superordinate regulator of transcription, inside the MHC-II region with specific impact on human leucocyte antigen (HLA) gene expression. In this prospective exploratory study, we investigated to which extent major surgery affects the MHC-II region of circulating CD14+-monocytes. RESULTS: In non-immunocompromised patients undergoing elective major abdominal surgery, a postoperative loss of monocyte HLA-DR surface receptor density was accompanied by a decline in the transcription levels of the classical MHC-II genes HLA-DRA, HLA-DRB1, HLA-DPA1 and HLA-DPB1. The surgical event decreased the expression of the transcriptional MHC-II regulators CIITA and CTCF and led to a lower CTCF enrichment at an intergenic sequence within the HLA-DR subregion. During the observation period, we found a slow and only incomplete restoration of monocyte HLA-DR surface receptor density as well as a partial recovery of CIITA, HLA-DRA and HLA-DRB1 expression. In contrast, transcription of HLA-DPA1, HLA-DPB1, CTCF and binding of CTCF within the MHC-II remained altered. CONCLUSION: In circulating monocytes, major surgery does not globally affect MHC-II transcription but rather induces specific changes in the expression of selected HLA genes, followed by differential recovery patterns and accompanied by a prolonged reduction of CTCF expression and binding within the MHC-II region. Our results hint toward a long-lasting impact of a major surgical intervention on monocyte functionality, possibly mediated by epigenetic changes that endure the life span of the individual cell.

Microcirculatory tissue oxygenation correlates with kidney function after transcatheter aortic valve implantation-Results from a prospective observational study.

Introduction: Kidney dysfunction is common in patients with aortic stenosis (AS) and correction of the aortic valve by transcatheter aortic valve implantation (TAVI) often affects kidney function. This may be due to microcirculatory changes. Methods: We evaluated skin microcirculation with a hyperspectral imaging (HSI) system, and compared tissue oxygenation (StO2), near-infrared perfusion index (NIR), tissue hemoglobin index (THI) and tissue water index (TWI) in 40 patients undergoing TAVI versus 20 control patients. HSI parameters were measured before TAVI (t1), directly after TAVI (t2), and on postinterventional day 3 (t3). The primary outcome was the correlation of tissue oxygenation (StO2) to the creatinine level after TAVI. Results: We performed 116 HSI image recordings in patients undergoing TAVI for the treatment of severe aortic stenosis and 20 HSI image recordings in control patients. Patients with AS had a lower THI at the palm (p = 0.034) and a higher TWI at the fingertips (p = 0.003) in comparison to control patients. TAVI led to an increase of TWI, but had no uniform enduring effect on StO2 and THI. Tissue oxygenation StO2 at both measurement sites correlated negatively with creatinine levels after TAVI at t2 (palm: ρ = -0.415; p = 0.009; fingertip: ρ = -0.519; p < 0.001) and t3 (palm: ρ = -0.427; p = 0.008; fingertip: ρ = -0.398; p = 0.013). Patients with higher THI at t3 reported higher physical capacity and general health scores 120 days after TAVI. Conclusion: HSI is a promising technique for periinterventional monitoring of tissue oxygenation and microcirculatory perfusion quality, which are related to kidney function, physical capacity, and clinical outcomes after TAVI. Clinical trial registration: https://drks.de/search/de/trial, identifier DRKS00024765.

Intranasal Lidocaine Administration via Mucosal Atomization Device: A Simple and Successful Treatment for Postdural Puncture Headache in Obstetric Patients.

(1) Background: Postdural puncture headache (PDPH) remains a serious complication in obstetric patients. While the epidural blood patch represents the current gold standard in therapy, a growing number of alternative measures are thought to be beneficial for clinical management. The purpose of this study was to retrospectively analyze the efficacy of intranasal lidocaine administration to treat PDPH in obstetrics at our university hospital; (2) Methods: A retrospective analysis of the medical records of patients with PDPH has been performed focusing on the techniques of administration, dosing, treatment duration, impact on pain intensity as well as side effects of intranasal lidocaine; (3) Results: During the study period, 5610 obstetric patients received neuraxial anesthesia, of whom 43 (0.77%) developed PDPH. About one third of the patients with PDPH after spinal anesthesia (n = 8), epidural anesthesia (n = 5) or both (n = 2) were treated with intranasal lidocaine. Lidocaine was administered either via gauze compresses (GC, n = 4), a mucosal atomization device (MAD, n = 8) or with a second-line mucosal atomization device due to low gauze compress efficacy (n = 3). All patients treated with lidocaine refused the epidural blood patch. Nebulization of lidocaine resulted in a significant reduction in pain intensity after the first dose (p = 0.008). No relevant side effects developed except sporadic temporal pharyngeal numbness. The utilization of the mucosal atomization device averted the necessity for an epidural blood patch, whether employed as the primary or secondary approach; (4) Conclusions: Our data imply that the mucosal atomization device enhances the efficacy of intranasal lidocaine administration in obstetric patients suffering from PDPH.

[Postdural puncture headache in obstetrics : Pathogenesis, diagnostics and treatment]. / Postpunktionskopfschmerz in der Geburtshilfe : Pathogenese, Diagnostik und Therapie.

Postdural puncture headache (PDPH) is one of the most important complications of peripartum neuraxial analgesia. Loss of cerebrospinal fluid volume and pressure as well as compensatory intracranial vasodilation are assumed to be responsible. Potentially severe long-term sequelae necessitate the correct diagnosis of PDPH, exclusion of relevant differential diagnoses (with atypical symptoms and when indicated via imaging techniques) and rapid initiation of effective treatment. Nonopioid analgesics, caffeine and occasionally theophylline, gabapentin and hydrocortisone are the cornerstones of pharmacological treatment, while the timely placement of an autologous epidural blood patch (EBP) represents the gold standard procedure when symptoms persist despite the use of analgesics. Procedures using neural treatment are promising alternatives, especially when an EBP is not desired by the patient or is contraindicated. Interdisciplinary and interprofessional consensus standard procedures can contribute to optimization of the clinical management of this relevant complication.

Early Use of Methylene Blue in Vasoplegic Syndrome: A 10-Year Propensity Score-Matched Cohort Study.

BACKGROUND: Vasoplegic syndrome is associated with increased morbidity and mortality in patients undergoing cardiac surgery. This retrospective, single-center study aimed to evaluate the effect of early use of methylene blue (MB) on hemodynamics after an intraoperative diagnosis of vasoplegic syndrome (VS). METHODS: Over a 10-year period, all patients diagnosed with intraoperative VS (hypotension despite treatment with norepinephrine ≥0.3 µg/kg/min and vasopressin ≥1 IE/h) while undergoing heart surgery and cardiopulmonary bypass were identified, and their data were examined. The intervention group received MB (2 mg/kg intravenous) within 15 min after the diagnosis of vasoplegia, while the control group received standard therapy. The two groups were matched using propensity scores. RESULTS: Of the 1022 patients identified with VS, 221 received MB intraoperatively, and among them, 60 patients received MB within 15 min after the diagnosis of VS. After early MB application, mean arterial pressure was significantly higher, and vasopressor support was significantly lower within the first hour (p = 0.015) after the diagnosis of vasoplegia, resulting in a lower cumulative amount of norepinephrine (p = 0.018) and vasopressin (p = 0.003). The intraoperative need of fresh frozen plasma in the intervention group was lower compared to the control group (p = 0.015). Additionally, the intervention group had higher creatinine values in the first three postoperative days (p = 0.036) without changes in dialysis incidence. The 90-day survival did not differ significantly (p = 0.270). CONCLUSION: Our results indicate the additive effects of MB use during VS compared to standard vasopressor therapy only. Early MB administration for VS may significantly improve the patients' hemodynamics with minor side effects.