Neurotoxicity of crack cocaine exposure: evidence from a systematic review of in vitro and in vivo studies.

Several studies suggest that crack cocaine users exhibit higher prevalence of both psychiatric and psychosocial problems, with an aggressive pattern of drug use. Nevertheless, few experimental studies attempted to verify the neurotoxicity after crack cocaine exposure, especially when compared with other routes of cocaine administration. This systematic review aimed to verify whether in vitro and/or in vivo crack cocaine exposure is more neurotoxic than cocaine exposure (snorted or injected). A search was performed in the PubMed, EMBASE, Scopus, Web of Science, and LILACS databases for in vitro and in vivo toxicological studies conducted with either rats or mice, with no distinction with regard to sex or age. Other methods including BioRxiv, BDTD, Academic Google, citation searching, and specialist consultation were also adopted. Two independent investigators screened the titles and abstracts of retrieved studies and subsequently performed full-text reading and data extraction. The quality of the included studies was assessed by the Toxicological data Reliability assessment Tool (ToxRTool). The study protocol was registered with the Prospective Registry of Systematic Reviews (PROSPERO; CRD42022332250). Of the twelve studies included, three were in vitro and nine were in vivo studies. According to the ToxRTool, most studies were considered reliable either with or without restrictions, with no one being considered as not reliable. The studies found neuroteratogenic effects, decreased threshold for epileptic seizures, schizophrenic-like symptoms, and cognitive deficits to be associated with crack cocaine exposure. Moreover, both in vitro and in vivo studies reported a worsening in cocaine neurotoxic effect caused by the anhydroecgonine methyl ester (AEME), a cocaine main pyrolysis product, which is in line with the more aggressive pattern of crack cocaine use. This systematic review suggests that crack cocaine exposure is more neurotoxic than other routes of cocaine administration. However, before the scarcity of studies on this topic, further toxicological studies are necessary.

The effect of preconditioning agents on cardiotoxicity and neurotoxicity of carbon monoxide poisoning in animal studies: a systematic review.

BACKGROUND: Carbon monoxide (CO) poisoning is a common intoxication and many people die yearly due to CO poisoning and preconditioning agents attenuate brain and cardiac injury caused by intoxication. It is critical to fully understand the efficacy of new methods to directly target the toxic effect of CO, such as conditioning agents, which are currently under development. This study aims to systematically investigate current evidence from animal experiments and the effects of administration preconditions in acute and late phases after CO poisoning on cardiotoxicity and neurotoxicity. METHODS: Four databases (PubMed, Embase, Scopus, and Web of Science) were systematically searched without language restrictions, and hand searching was conducted until November 2021. We included studies that compare preconditioning agents with the control group after CO poisoning in animals. The SYRCLE RoB tool was used for risk of bias assessments. RESULTS: Thirty-seven studies were included in the study. Erythropoietin, granulocyte colony-stimulating factor (GCSF), hydrogen-rich saline, and N-butylphthalide (NBP) were found to have positive effects on reducing neurotoxicity and cardiotoxicity. As other preconditions have fewer studies, no valuable results can be deduced. Most of the studies were unclear for sources of bias. DISCUSSION: Administration of the examined preconditioning agents including NBP, hydrogen-rich saline, and GCSF in acute and late phases could attenuate neurotoxicity and cardiotoxicity of CO poisoned animals. For a better understanding of mechanisms and activities, and finding new and effective preconditioning agents, further preclinical and clinical studies should be performed to analyze the effects of preconditioning agents.

Interval-dependent neurotoxicity after multiple ketamine injections in late postnatal mice.

PURPOSE: Measuring the neurotoxic effects of multiple anesthetic exposures during neurodevelopment is complex due to the numerous factors that can affect the outcome. While we recently discovered that the interval between multiple sevoflurane exposures can affect the level of neurotoxicity, the significance of interval for other anesthetic agents is unknown. Thus, we evaluated the significance of dosing interval in the neurotoxic effects of multiple ketamine injections in postnatal day (PND) 17 mice. METHODS: PND17 mice of both sexes were intraperitoneally injected with ketamine (35 mg/kg) three times at short (2 h) or long (24 h) intervals. Changes in synaptic transmission were measured in hippocampal pyramidal neurons 5 days after the last injection, and behavioral changes were assessed at the age of 8 weeks. Values are presented as mean ± SD. RESULTS: Whereas short-interval ketamine injections enhanced excitatory synaptic transmission, as evidenced by an increased frequency of miniature excitatory postsynaptic currents (mEPSCs; ketamine, 0.09 ± 0.07 Hz; control, 0.06 ± 0.03 Hz), long-interval ketamine injections did not; instead, they decreased the amplitude of miniature inhibitory postsynaptic currents (mIPSCs; ketamine, 47.72 ± 6.90 pA; control, 51.21 ± 7.65 pA,). However, only long-interval ketamine injections induced long-term changes in anxiety behavioral in the open-field test (decrease in center duration; ketamine, 400.1 ± 162.8 s; control, 613.3 ± 312.7 s). CONCLUSIONS: Multiple ketamine injections induce interval-dependent, long-lasting synaptic changes and behavioral impairments. Future studies should carefully consider the dosing interval as a significant factor when studying the neurotoxic effects of multiple anesthetic exposures.

FLOX (5-fluorouracil + leucovorin + oxaliplatin) chemotherapy for colorectal cancer leads to long-term orofacial neurotoxicity: a STROBE-guided longitudinal prospective study.

BACKGROUND: Colorectal carcinoma (CRC) is widely treated by chemotherapy based on an intensely neurotoxic drug: oxaliplatin (OXL). We objective to evaluate prospectively the orofacial neurotoxicity during FLOX (fluorouracil + leucovorin + OXL) chemotherapy. METHODS: So, 46 patients with CRC were prospectively evaluated during FLOX chemotherapy by 3 cycles (C) of 6 weeks (W) each. We weekly applied the orofacial section of the Acute and Chronic Neuropathy Questionnaire of Common Toxicity Criteria for Adverse Events of the National Cancer Institute of the United States of America (Oxaliplatin-specific neurotoxicity scale). Patients were asked the following concerning the severity (scores 0-5) of orofacial symptoms: jaw pain, eyelids drooping, throat discomfort, ear pain, tingling in mouth, difficulty with speech, burning or discomfort of the eyes, loss of any vision, feeling shock/pain down back and problems breathing. We summed the scores (0-50) and evaluated the clinicopathological data. Friedman/Dunn, Chi square and multinomial regression logistic tests were used (SPSS 20.0, p < 0.05). RESULTS: There was a significant increase in sum of orofacial neurotoxicity from baseline to C1.W3, C2.W1 and C3.W5 (p < 0.001) due increase in scores of jaw pain (p < 0.001), eyelids drooping (p = 0.034), throat discomfort (p < 0.001), ear pain (p = 0.034), tingling in mouth (p = 0.015), burning/discomfort of your eyes (p < 0.001), loss of any vision (p < 0.001), feeling shock/pain down back (p < 0.001), problems with breathing (p = 0.045), but not difficulty with speech (p = 0.087). Women (p = 0.021) and young patients (p = 0.027) had significant higher prevalence of orofacial neurotoxicity. CONCLUSIONS: FLOX-related orofacial neurotoxicity begins acutely and remains long term with increased incidence in women and younger patients.

Persistent taxane-induced neuropathy in elderly patients treated for localized breast cancer.

Breast cancer is the most common cancer among women. Localized breast cancer treatments involve taxanes which are often responsible for acute peripheral neuropathy. The persistence of taxane-induced peripheral neuropathy (TIPN) is scarcely described among elderly women. A monocenter historical cohort study including all women over 65 years of age treated between 2001 and 2016 with a taxane-based chemotherapy for localized breast cancer was carried out at the Paul Strauss Regional Comprehensive Cancer Center. All cases included were followed up for at least 2 years, deaths from causes unrelated to TIPN were excluded. We report on the frequency and risk factors and establish a prognostic score of persistent Common Terminology Criteria for Adverse Events (CTCAE) grade 2 and 3 TIPN. Among the 302 included patients, 21% and 9% developed persistent TIPN of grade 2 and 3, respectively. Two patients died from complications of grade 3 TIPN. Risk factors of persistent grade 2 and higher neuropathy included age (P < .0001), body mass index (P < .0001), and diabetes (P = .0093). Persistent TIPN was more frequent with paclitaxel than docetaxel (OR = 5.43; P < .0001). Patients presenting all four major risk factors had a 97.2% probability of developing long-term symptoms against 1.2% for patients showing no risk factor. We therefore identified 3 prognostic groups. TIPN is a frequent and sometimes severe persistent side effect of breast cancer treatment among elderly women with a major impact on health-related quality of life. Chemotherapy regimens without taxane could therefore be a valid option in elderly patients with neurotoxicity risk factors.

Should nitrous oxide ever be used in oncology patients receiving methotrexate therapy?

Nitrous oxide (N2 O) is frequently used for short anesthesia/analgesia in children undergoing painful or repetitive procedures. Children with acute lymphoblastic leukemia (ALL) require repeated lumbar punctures with direct instillation of intrathecal chemotherapy, usually the anti-folate agent methotrexate, during their treatment. These procedures are frequently performed under anesthesia. Concerns have been intermittently raised about a drug interaction between methotrexate and N2 O that may potentiate the undesirable side effects of methotrexate, including neurotoxicity. However, the clinical evidence consists mainly of isolated case reports leading to a lack of consensus among pediatric anesthetists about the relative risk benefits of using N2 O in children with ALL. In this article, we review the biochemical basis and scientific observations that suggest a significant interaction between N2 O and methotrexate due to their dual inhibition of the key enzyme methionine synthase. The possible role of this interaction in potentiating neurotoxicity in children with cancer is discussed, and arguments and counterarguments about the clinical significance of this largely theoretical relationship are explored. Following comprehensive review of all the available data, we make the case for the circumstantial evidence being sufficiently compelling to prompt a review of practice by pediatric anesthetists and call for a precautionary approach by avoiding the use of N2 O in children receiving concurrent methotrexate.

Hydromorphone-induced chorea as an atypical presentation of opioid neurotoxicity: A case report and review of the literature.

BACKGROUND: While opioid-induced myoclonus is well described, there are limited reports of opioid-induced chorea. Here we present the first case of chorea as a manifestation of opioid neurotoxicity due to hydromorphone. CASE PRESENTATION: A 20-year-old woman presenting with fevers and cutaneous lesions was diagnosed with hemophagocytic lymphohistiocytosis secondary to primary cutaneous lymphoma. Surgical resection of a cutaneous lesion was complicated by severe postoperative pain requiring rapid opioid dose escalation. Seven days after hydromorphone was initiated, she developed positive myoclonus, hallucinations, delirium, and involuntary, flowing movements consistent with chorea. She had no personal or family history of nervous system disorders and was not taking any medications associated with drug-induced chorea. Case management: The remainder of her neurologic examination was unremarkable. Her renal function was normal and no etiology was found on neuroimaging or laboratory workup. Hydromorphone was discontinued and pain control was achieved with fentanyl. Case outcome: The patient's neurotoxic symptoms including chorea resolved within 72 h of hydromorphone discontinuation. CONCLUSION: Further studies are needed to determine which patients have a unique sensitivity to opioids predisposing them to chorea. Clinicians should be aware that chorea may be a sign of such toxicity so that rapid corrective action can be taken.

Visual recognition memory is impaired in rhesus monkeys repeatedly exposed to sevoflurane in infancy.

BACKGROUND: Experimental studies in animals have shown that exposure to general anaesthesia in infancy can cause loss of cells in the central nervous system and long-term impairments in neurocognitive function. Some human epidemiological studies have shown increased risk of learning disability after repeated anaesthesia exposure in early childhood. Thus, we investigated in a highly translational rhesus monkey model, whether repeated exposure in infancy to the inhalation anaesthetic sevoflurane is associated with impaired visual recognition memory during the first two yr of life. METHODS: Rhesus monkeys of both sexes were exposed to sevoflurane inhalation anaesthesia on approximately postnatal day 7 and then again 14 and 28 days later, for four h each time. Visual recognition memory was tested using the visual paired comparison task, which measures memory by assessing preference for looking at a new image over a previously-viewed image. Monkeys were tested at 6-10 months of age, again at 12-18 months of age, and again at 24-30 months of age. RESULTS: No memory impairment was detected at 6-10 months old, but significant impairment (reduced time looking at the novel image) was observed at 12-18 and 24-30 months old. CONCLUSIONS: Repeated exposure of infant rhesus monkeys to sevoflurane results in visual recognition memory impairment that emerges after the first yr of life. This is consistent with epidemiological studies that show increased risk of learning disability after repeated exposure to anaesthesia in infancy/early childhood. Moreover, these deficits may emerge at later developmental stages, even when memory performance is unaffected earlier in development.

Risk factors of ifosfamide-related encephalopathy in adult patients with cancer: A retrospective analysis.

BACKGROUND/PURPOSE: Ifosfamide, a widely used chemotherapeutic agent, has been frequently associated with encephalopathy. A larger-scale study was conducted to identify risk factors of ifosfamide-related encephalopathy, including hepatic function. METHODS: Adult patients who had completed at least one cycle of ifosfamide between January 2008 and December 2010 were included. Those with renal failure or liver failure were excluded. Data were collected through chart review. Patients with encephalopathy and patients without encephalopathy were compared on age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), baseline serum creatinine (SCr) level, albumin level, white blood cell count, liver function, brain metastasis, and dosage of ifosfamide. Chi-square test or Fisher's exact test, Student t test, and univariate and multivariate logistic regressions were used for analysis. RESULTS: This study enrolled 337 patients. Thirty-eight patients (11%) had ifosfamide-related encephalopathy. They had poorer ECOG PS; higher SCr level, white blood cell count, and aspartate aminotransferase level; and lower serum albumin level compared with patients without encephalopathy. Ifosfamide dosage, brain metastasis, and age were not significant risk factors. Multivariate analysis indicated that only ECOG PS, SCr level, and albumin level contributed significantly to the risk. CONCLUSION: To date, this is the largest-scale study to have analyzed the risk factors of ifosfamide-related encephalopathy. This study confirms that an ECOG PS of 2-4 and increased SCr level are significant risk factors of ifosfamide-related encephalopathy, whereas increased albumin level decreases the risk, consistent with previous reports. Higher aspartate aminotransferase levels have no significant impact. In contrast to previous studies, ifosfamide dosage and brain metastasis are not significant contributing factors.

A comparison of functional magnetic resonance imaging findings in children with and without a history of early exposure to general anesthesia.

BACKGROUND: Functional magnetic resonance imaging (fMRI) has been used to evaluate the long-term consequences of early exposure to neurotoxic agents. fMRI shows that different patterns of brain activation occur in ethanol-exposed subjects performing a go/no-go response inhibition task. Pharmacologically, ethanol and general anesthetics have similar receptor-level activity in the brain. This study utilizes fMRI to examine brain activation patterns in children exposed to general anesthesia and surgery during early brain development. METHODS: After obtaining Nationwide Children's Hospital IRB approval, a surgical database was utilized to identify children aged 10-17 years with a history of at least 1 h of exposure to general anesthetics and surgery when they were between 0 and 24 months of age. Age- and gender-matched children without anesthesia exposure were recruited as a control group. All subjects were scanned while being presented with a go/no-go response inhibition task. Reaction time and accuracy data were acquired, and the blood-oxygen-level-dependent (BOLD) fMRI signal was measured as a biomarker for regional neuronal activity. RESULTS: There were no differences in terms of performance accuracy and response time. The analysis did not reveal any significant activation differences in the primary region of interest (prefrontal cortex and caudate nucleus); however, activation differences were seen in other structures, including the cerebellum, cingulate gyrus, and paracentral lobule. CONCLUSIONS: Early anesthetic exposure and surgery did not affect accuracy, response time, or activation patterns in the primary region of interest during performance of the task. Intergroup differences in activation patterns in other areas of the brain were observed, and the significance of these findings is unknown. fMRI appears to be a useful tool in evaluating the long-term effects of early exposure to general anesthesia.

Anesthetic neurotoxicity: what to tell the parents?

Over the past decade, numerous preclinical and retrospective human studies have reported that the provision of anesthetic and sedative agents to infants and children may be associated with adverse neurodevelopmental outcomes. These data have gained widespread attention from professional and regulatory agencies, including the public at large. As such, pediatric anesthesiologists are being increasingly questioned by parents about the risks of anesthetic agents on their children's neurocognitive development. To impart a framework from which anesthesiologists may address the apprehensions of parents who actively bring up this issue, we review the data supporting anesthetic neurotoxicity and discuss its strengths and limitations. As many parents are not yet aware and do not actively raise these concerns, we also discuss whether such a conversation should be undertaken as a part of the consent process.

Transient cortical weakness following cerebral angiography: A new syndrome.

Transient cortical blindness is a known complication of iodinated contrast administration and is believed to reflect osmotic injury or autoregulatory dysfunction of the posterior circulation. Here, we report 2 cases of postangiography transient cortical weakness, a rare clinical analog to transient cortical blindness that affects the anterior circulation. The symptoms, timeline, and imaging findings of transient cortical weakness are distinct from more common post-procedural complications such as acute ischemic stroke or transient ischemic attack.

Inhibition of the glutamatergic PVT-NAc projections attenuates local anesthetic-induced neurotoxic behaviors.

INTRODUCTION: Local anesthetic-induced neurotoxicity contributes to perioperative nerve damage; however, the underlying mechanisms remain unclear. Here, we investigated the role of the paraventricular thalamus (PVT)-nucleus accumbens (NAc) projections in neurotoxicity induced by ropivacaine, a local anesthetic agent. METHODS: Ropivacaine (58 mg/kg, intraperitoneal administration) was used to construct the local anesthetic systemic toxicity (LAST) mice model. We first identified neural projections from the PVT to the NAc through the expression of a retrograde tracer and virus. The inhibitory viruses (rAAV-EF1α-DIO-hm4D(Gi)-mCherry-WPREs: AAV2/retro and rAAV-CaMKII-CRE-WPRE-hGh: AAV2/9) were injected into the mice model to assess the effects of the specific inhibition of the PVT-NAc pathway on neurological behaviors in the presence of clozapine-N-oxide. The inhibition of the PVT-NAc pathway was evaluated by immunofluorescence staining of c-Fos-positive neurons and Ca2+ signals in CaMKIIa neurons. RESULTS: We successfully identified a circuit connecting the PVT and NAc in C57BL/6 mice. Ropivacaine administration induced the activation of the PVT-NAc pathway and seizures. Specific inhibition of NAc-projecting CaMKII neurons in the PVT was sufficient to inhibit the neuronal activity in the NAc, which subsequently decreased ropivacaine-induced neurotoxicity. CONCLUSION: These results reveal the presence of a dedicated PVT-NAc circuit that regulates local anesthetic-induced neurotoxicity and provide a potential mechanistic explanation for the treatment and prevention of LAST.

The lateral septum partakes the regulation of propofol-induced anxiety-like behavior.

Repeated exposure to propofol during early brain development is associated with anxiety disorders in adulthood, yet the mechanisms underlying propofol-induced susceptibility to anxiety disorders remain elusive. The lateral septum (LS), primarily composed of γ-aminobutyric acidergic (GABAergic) neurons, serves as a key brain region in the regulation of anxiety. However, it remains unclear whether LS GABAergic neurons are implicated in propofol-induced anxiety. Therefore, we conducted c-Fos immunostaining of whole-brain slices from mice exposed to propofol during early life. Our findings indicate that propofol exposure activates GABAergic neurons in the LS. Selective activation of LS GABAergic neurons resulted in increased anxiety-like behavior, while selective inhibition of these neurons reduced such behaviors. These results suggest that the LS is a critical brain region involved in propofol-induced anxiety. Furthermore, we investigated the molecular mechanism of propofol-induced anxiety in the LS. Microglia activation underlies the development of anxiety. Immunofluorescence staining and Western blot analysis of LS revealed activated microglia and significantly elevated levels of phospho-NF-κB p65 protein. Additionally, a decrease in the number of neuronal spines was observed. Our study highlights the crucial role of the LS in the development of anxiety-like behavior in adulthood following childhood propofol exposure, accompanied by the activation of inflammatory pathways.

Attenuation of acrylamide-induced neurotoxicity by supplementation of sitagliptin in Wistar rats.

Objectives: Acrylamide (ACR) induces neurotoxicity in humans and animals through different mechanisms. Sitagliptin is a type-2 diabetes medication with neuroprotective properties. The effects of sitagliptin against neurotoxicity stimulated by ACR were examined. Materials and Methods: Male Wistar rats were classified as follows: 1. Control (normal saline, 11 days, IP), 2. ACR (50 mg/kg, 11 days, IP), 3. ACR (11 days, days 11-20 normal saline), 4-7. ACR+sitagliptin (5, 10, 20, and 40 mg/kg, 11 days, IP), 8. ACR+sitagliptin (10 mg/kg, days 6-11), 9. ACR+sitagliptin (10 mg/kg, days 6-20), 10. Sitagliptin (40 mg/kg, 11 days), 11. ACR+vitamin E (200 mg/kg, IP). Finally, the gait score was evaluated. Reduced glutathione (GSH) and malondialdehyde (MDA) levels were measured in cortex tissue. Also, IL-1ß, TNF-α, and caspase-3 levels were assessed in the cortex by western blotting. Results: ACR caused movement disorders, triggered oxidative stress, and raised TNF-α, IL-1ß, and caspase-3 cleaved levels. Supplementation of sitagliptin (10 mg/kg) along with ACR, in 3 protocols, reduced gait disorders compared to the ACR group. Receiving sitagliptin in all doses plus ACR and injection of sitagliptin (10 mg/kg) from days 6 to11 reduced the MDA level of cortex tissue. Sitagliptin (all doses) plus ACR increased the GSH level of the cortex tissue. Sitagliptin (10 mg/kg) with ACR dropped the amounts of TNF-α and caspase-3 cleaved proteins in cortex tissue but did not affect the IL-1ß level. Conclusion: Sitagliptin disclosed preventive and therapeutic effects on ACR neurotoxicity. Sitagliptin possesses antioxidant, anti-inflammatory, and anti-apoptotic properties and inhibits CR neurotoxicity in rats.

Anesthetic neurotoxicity in the developing brain: an update on theinsights and implications for fetal surgery.

This review describes an in-depth analysis of the neurotoxicity associated with the anesthetic agents used during fetal surgery, intending to highlight the importance of understanding the effects of general anesthetics on the developing brain, particularly in the context of open fetal surgery, where high doses are applied to facilitate surgical access and augment uterine relaxation. We examined evidence from preclinical studies in rodents and primates, along with studies in human subjects, with the results collectively suggesting that general anesthetics can disrupt brain development and lead to long-lasting neurological deficits. Our review underscores the clinical implications of these findings, indicating an association between extensive anesthetic exposure in early life and subsequent cognitive deficits. The current standard of anesthetic care for fetal surgical procedures was scrutinized, and recommendations have been proposed to mitigate the risk of anesthetic neurotoxicity. These recommendations emphasize the need for careful selection of anesthetic techniques to minimize fetal exposure to potentially harmful agents. In conclusion, while the benefits of fetal surgery in addressing immediate risks often outweigh the potential neurotoxic effects of anesthesia, the long-term developmental impacts nevertheless warrant consideration. Our analysis suggests that the use of general anesthetics in fetal surgery, especially at high doses, poses a significant risk of developmental neurotoxicity. As such, it is imperative to explore safer alternatives, such as employing different methods of uterine relaxation and minimizing the use of general anesthetics, to achieve the necessary surgical conditions. Further research, particularly in clinical settings, is essential to fully understand the risks and benefits of anesthetic techniques in fetal surgery.

Prolonged administration of intrathecal baclofen in a patient with generalized grade 4 tetanus.

INTRODUCTION: This case report presents the management of a 62-year-old woman with generalized grade 4 tetanus, focusing on the innovative use of intrathecal baclofen (ITB) therapy. The patient initially presented with a laceration and subsequently developed severe tetanic spasms, necessitating interventions beyond standard tetanus immunoglobulin and antibiotics due to the condition's progressive and life-threatening nature. The preference for ITB over oral baclofen is highlighted, considering ITB's enhanced bioavailability in the central nervous system and its efficacy in reducing spinal cord reflexes, which is critical for managing severe spasticity.On her return to the emergency department with symptoms of tetanus, the patient received ITB following the failure of oral baclofen to control the spasms. ITB administration necessitated a lumbar drain, which was later substituted with a tunneled intrathecal catheter due to the extended requirement for baclofen infusion and the unavailability of suitable infusion pumps. This scenario represented a significant application of a CADD-Solis external pump for continuous ITB infusion.Transitioning the patient from ITB to oral baclofen was a crucial management step to facilitate discharge and recovery, underscoring the importance of a careful approach to prevent withdrawal symptoms and maintain care continuity. Despite initial complications, including an infection signaled by leucocytosis and confirmed through cerebrospinal fluid culture, the patient was effectively treated and discharged. CONCLUSION: This report contributes to the sparse literature on prolonged ITB use for generalized grade 4 tetanus treatment, underlining the need for interdisciplinary collaboration for the best patient outcomes. It showcases the potential of ITB in spasticity management, in reducing the need for sedation, and in shortening the duration of mechanical ventilation, advocating for a tailored approach that utilizes a full spectrum of pharmacological and supportive therapies.

Acute reversal of respiratory distress after a preoperative single-shot interscalene nerve block.

BACKGROUND: Diaphragmatic paresis is a known complication of the interscalene block used for postoperative analgesia in shoulder surgery. A technique involving the injection of normal saline through the interscalene catheter to alleviate this condition has shown promise. This method, termed the "washing-off" technique, dilutes the local anesthetic around the phrenic nerve, mitigating respiratory symptoms. CASE PRESENTATION: A 65-year-old male patient with multiple comorbidities (American Society of Anesthesiologists physical status classification 4) was scheduled for arteriovenous brachiocephalic fistula creation under regional anesthesia. Following an interscalene block with 32 mL of mepivacaine 1.5%, the patient experienced acute respiratory distress, with SpO2 at 88% despite 6 L O2 via nasal cannula. To avoid intubation, a 20 mL normal saline injection was administered through single-shot interscalene injection under ultrasound guidance. Within 5 min, respiratory distress markedly improved, allowing the patient to converse. Surgery proceeded without complications, maintaining SpO2 at 99% with 6 L O2. Postoperatively, the patient remained stable, with SpO2 at 98% on 2 L O2, and was discharged from the recovery room without additional oxygen requirements. CONCLUSIONS: The "washing-off" technique's mechanism may involve dilutional effects, pH changes or local sodium concentration alterations affecting the phrenic nerve. This case demonstrates its effectiveness in an acute setting, enabling surgery under regional anesthesia without intubation or any additional analgesia. The previously considered placebo effect appears unlikely here.