Erector Spinae Plane (ESP) Block for Postoperative Pain Management after Open Oncologic Abdominal Surgery.

Patients undergoing abdominal oncologic surgical procedures require particular surgical and anesthesiologic considerations. Traditional pain management, such as opiate treatment, continuous epidural analgesia, and non-opioid drugs, may have serious side effects in this patient population. We evaluated erector spinae plane (ESP) blocks for postoperative pain management following elective oncologic abdominal surgeries. In this single-center, prospective, and randomized study, we recruited 100 patients who underwent elective oncological abdominal surgery between December 2020 and January 2022 at Soroka University Medical Center in Beer Sheva, Israel. We compared postoperative pain levels in patients who were treated with a preincisional ESP block in addition to traditional pain management with intravenous opioids, non-steroidal anti-inflammatory drugs (NSAIDs), and acetaminophen, compared to patients who were only given traditional pain management (control). Patients who were treated with a preincisional ESP block demonstrated significantly lower Visual Analog Scale scores at 60 minutes and 4, 8, and 12 hours following the surgery, compared to the control group (p < 0.001). Accordingly, patients in the ESP group required less morphine from 60 minutes to 12 hours after surgery, but they required increased non-opioid postoperative analgesia management at 4, 8, and 12 hours after surgery (p from 0.002 to <0.001) compared to the control group. In this study, we found ESP blocks to be a safe, technically simple, and effective treatment for postoperative pain management after elective oncologic abdominal procedures.

Blood Glutamate Scavenging With Pyruvate as a Novel Preventative and Therapeutic Approach for Depressive-Like Behavior Following Traumatic Brain Injury in a Rat Model.

Depression is a common and serious complication following traumatic brain injury (TBI). Both depression and TBI have independently been associated with pathologically elevated extracellular brain glutamate levels. In the setting of TBI, blood glutamate scavenging with pyruvate has been widely shown as an effective method to provide neuroprotection by reducing blood glutamate and subsequent brain glutamate levels. Here we evaluate pyruvate as a novel approach in the treatment and prevention of post-TBI depression-like behavior in a rat model. Rats were divided into five groups: (1) sham-operated control with pyruvate, (2) sham-operated control with placebo, (3) post-TBI with placebo, (4) post-TBI given preventative pyruvate, and (5) post-TBI treated with pyruvate. These groups had an equal number of females and males. Rats were assessed for depressive-like behavior, neurological status, and glutamate levels in the blood and brain. Post-TBI neurological deficits with concurrent elevations in glutamate levels were demonstrated, with peak glutamate levels 24 h after TBI. Following TBI, the administration of either prophylactic or therapeutic pyruvate led to reduced glutamate levels, improved neurologic recovery, and improved depressive-like behavior. Glutamate scavenging with pyruvate may be an effective prophylactic and therapeutic option for post-TBI depression by reducing associated elevations in brain glutamate levels.

Serratus Anterior Block for Long-Term Post-Thoracoscopy Pain Management.

PURPOSE: Neuropathic, chronic pain is a common and severe complication following thoracic surgery, known as post-thoracotomy pain syndrome (PTPS). Here we evaluated the efficacy of an ultrasound-guided serratus anterior plane block (SAPB) on pain control compared to traditional pain management with intravenous opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) six months after thoracic surgery. PATIENTS AND METHODS: In this retrospective observational study, we analyzed data from a questionnaire survey. We interviewed all patients who underwent elective video-assisted thoracoscopy surgery (VATS) at Soroka University Medical Center between December 2016 and January 2018. The responses of ninety-one patients were included. RESULTS: Participants reported PTPS in both groups, 43% of patients in the SAPB group and 57% of patients in the standard group, which failed to reach significance. However, we demonstrated that the percentage of pain occurrence trended lower in the SAPB group. There was significantly less burning/stitching or shooting, shocking, pressure-like, and aching pain in SAPB patients compared to the standard protocol group. Patients in the SAPB group had significantly less pain located in the upper and lower posterior thorax anatomical regions compared to the standard protocol group. Moreover, we found a significant difference in occurrence of PTPS depending on the type of thoracic surgery. From both study groups, 69% of patients who underwent lobectomy reported pain, compared with 41.9% of those in the segmental (wedge resection) procedure, and 42.1% of patients in other procedures. CONCLUSION: While the present study did not demonstrate a statistically significant reduction of PTPS after SAPB concerning postoperative pain control, there was a trend of a decrease. We also found significance in the type of pain and location of pain after thoracic surgery between the two groups, as well as a significant difference between pain occurrence in types of thoracic surgeries from both groups.

A Complex Diving-For-Food Task to Investigate Social Organization and Interactions in Rats.

For many species, where status is a vital motivator that can affect health, social hierarchies influence behavior. Social hierarchies that include dominant-submissive relationships are common in both animal and human societies. These relationships can be affected by interactions with others and with their environment, making them difficult to analyze in a controlled study. Rather than a simple dominance hierarchy, this formation has a complicated presentation that allows rats to avoid aggression. Status can be stagnant or mutable, and results in complex societal stratifications. Here we describe a complex diving-for-food task to investigate rodent social hierarchy and behavioral interactions. This animal model may allow us to assess the relationship between a wide range of mental illnesses and social organization, as well as to study the effectiveness of therapy on social dysfunction.

A Metric Test for Assessing Spatial Working Memory in Adult Rats following Traumatic Brain Injury.

Impairments to sensory, short-term, and long-term memory are common side effects after traumatic brain injury (TBI). Due to the ethical limitations of human studies, animal models provide suitable alternatives to test treatment methods, and to study the mechanisms and related complications of the condition. Experimental rodent models have historically been the most widely used due to their accessibility, low cost, reproducibility, and validated approaches. A metric test, which tests the ability to recall the placement of two objects at various distances and angles from one another, is a technique to study impairment in spatial working memory (SWM) after TBI. The significant advantages of metric tasks include the possibility of dynamic observation, low cost, reproducibility, relative ease of implementation, and low stress environment. Here, we present a metric test protocol to measure impairment of SWM in adult rats after TBI. This test provides a feasible way to evaluate physiology and pathophysiology of brain function more effectively.

A Middle Cerebral Artery Occlusion Technique for Inducing Post-stroke Depression in Rats.

Post-stroke depression (PSD) is the most recurrent of all psychiatric complications resulting from an ischemic stroke. A greater majority (about 60%) of all ischemic stroke patients suffer from PSD, a disorder considered to be an ischemic stroke-related precursor for increased death and degradation in health. The pathophysiology of PSD is still obscure. To study the mechanism of development and occurrence of PSD further, and to find out a therapy, we attempted to develop a new protocol that requires occluding the middle cerebral artery (MCA) via the internal carotid artery (ICA) in rats. This protocol describes a model of PSD induced in rats through the middle cerebral artery occlusion (MCAO). Also used in the experiment are the Porsolt forced swim test and the sucrose preference test to confirm and evaluate the depressive mood of the rats under investigation. Rather than inserting the catheter through the external carotid artery (ECA), as stipulated for the original procedure, this MCAO technique has the monofilament passing directly through the ICA. This MCAO technique was developed a few years ago and leads to a reduction in mortality and variability. It is generally accepted that the criteria used are preferred in the selection of biological models. The data obtained with this protocol show that this model of MCAO could be a way of inducing PSD in rats and could potentially lead to the understanding of the pathophysiology and the future development of new drugs and other neuroprotective agents.

Ultrasound-guided serratus anterior plane block for analgesia after thoracic surgery.

BACKGROUND: Patients who undergo surgical procedures that impair the integrity of the chest wall frequently experience extremely severe postoperative pain. Opiates and weaker analgesics, such as nonsteroidal anti-inflammatory drugs (NSAIDs), are not sufficiently effective in achieving control of severe pain and might cause respiratory and gastrointestinal complications. In the past decade, there has been an increased interest in the use of regional nerve blocks for post-thoracoscopy and post-thoracotomy analgesia. METHODS: This is a prospective, randomized, double-blind and single-center study. We recruited 104 patients who underwent elective thoracoscopy. Prior to surgery, the participating patients were randomized into one of two study groups: Group 1- the "standard control group" that received standard postoperative pain control with intravenous opioids, NSAIDs and acetaminophen (paracetamol) and Group 2- the "block group" that was treated by ultrasound-guided serratus anterior plane (SAP) block (a single injection of 0.25% bupivacaine hydrochloride 2 mg/kg plus dexamethasone 8 mg) with standard postoperative pain control regimen. We compared the clinical, laboratory, and postoperative pain assessment data of both groups. RESULTS: Patients in the SAP block Group 2 reported significantly lower levels of pain after thoracic surgery as assessed by their visual analog scale scores, as compared to the patients in the standard pain control Group 1 (P<0.001). The total dosage of morphine and tramadol required for pain relief during the first hours after surgery was significantly lower in the patients who received SAP block. Also, the incidence of vomiting after surgery was significantly lower among the patients who received SAP block than among the patients who received standard pain control. CONCLUSION: The results of the present study suggest that SAP block is an effective adjuvant treatment option for post-thoracic surgery analgesia. Compared to the current methods used for post-thoracic surgery pain relief, SAP block has some significant merits, particularly its ease of use and its low potential for side effects.

Anatomical location of arterial and venous lines significantly affects motor performance in rats.

Several motor-function scales have been developed to assess neurological function in animal models of stroke, subarachnoid hemorrhage and closed head injury. We hypothesize that the location of arterial and venous catheters, even in the absence of brain injury, may impact rats' motor performance. Our study examined the effect of catheter location, rate of infection and the time required for catheter placement. We further describe an original technique of tail artery cannulation without exposure of the artery. Sixty-one rats were anesthetized and randomly assigned to one of seven groups, including no catheter, tail artery or artery + vein catheters, or femoral artery or artery + vein catheters. A neurological severity score (NSS) was determined at 1 h, 24 h and 48 h after surgical preparation or catheter placement. NSS at 1 h after placement of unilateral and bilateral femoral catheters was higher than the NSS observed at 1 h after placement of tail arterial and venous catheters (P < 0.01). The NSS also was higher at 24 h in the bilateral femoral catheter groups as compared with the tail catheter groups (P < 0.05). There were no differences in the NSS observed between the groups that had tail catheters and the sham group at 1 h, 24 h or 48 h. Infection rate at the site of catheter placement and the time required for catheter placement was also higher in the femoral catheter groups (P < 0.001). Thus, we propose that the line location may bias a study's results and lead to deceptive interpretations of neurological assessment following rat head injury. Compared to femoral vessels, tail blood vessels are preferable locations for lines placement.

Novel use of an exchange catheter to facilitate intubation with an Aintree catheter in a tall patient with a predicted difficult airway: a case report.

INTRODUCTION: The Aintree intubating catheter (Cook® Medical Inc., Bloomington, IN, USA) has been shown to successfully facilitate difficult intubations when other methods have failed. The Aintree intubating catheter (Cook® Medical Inc., Bloomington, IN, USA) has a fixed length of 56 cm, and it has been suggested in the literature that it may be too short for safe use in patients who are tall. CASE PRESENTATION: We present the case of a 32-year-old, 180 cm tall Caucasian woman with a predicted difficult airway who presented to our facility for an emergency cesarean section. After several failed intubation attempts via direct laryngoscopy, an airway was established with a laryngeal mask airway. After delivery of a healthy baby, our patient's condition necessitated tracheal intubation. A fiber-optic bronchoscope loaded with an Aintree intubating catheter (Cook® Medical Inc., Bloomington, IN, USA) was passed through the laryngeal mask airway into the trachea until just above the carina, but was too short to safely allow for the passage of an endotracheal tube. CONCLUSIONS: We present a novel technique in which the Aintree intubating catheter (Cook® Medical Inc., Bloomington, IN, USA) was replaced with a longer (100 cm) exchange catheter, over which an endotracheal tube was passed successfully into the trachea.

Effects of strong physical exercise on blood glutamate and its metabolite 2-ketoglutarate levels in healthy volunteers.

Excessive concentrations of L-glutamate (glutamate) have been found to posses neurotoxic properties. This study investigates how stress induced by strong physical exercise effects blood glutamate, 2-ketoglutarate, Alanine aminotransferase (ALT) and Aspartate Aminotransferase (AST) levels. The relationship between muscle damage caused by strong physical exercise and blood glutamate levels was also examined. Twenty-two healthy volunteers engaged in intense veloergometry ("spinning") for a duration of 60 minutes. Two 10 minute peaks of extremely intense exercise were performed at 10 minutes and 50 minutes after the start of exercise. After 60 minutes of exercise, volunteers were monitored for an additional 180 minutes in resting conditions. Blood samples for determination of glutamate and 2-ketoglutarate levels were collected prior to exercise and then every 30 min for entire experiment. Blood samples were also taken at those time points to measure glutamate, 2-ketoglutarate, AST, ALT, creatine phosphokinase (CPK), myoglobin, lactate and venous blood gas levels. Blood glutamate levels were significantly elevated throughout the exercise session (P less than 0.001) and then returned to baseline levels at the cessation of exercise. 2-ketoglutarate, a product of glutamate metabolism, reached significantly elevated levels at 30 minutes (P less than 0.01) from the start of exercise and remained elevated up to 240 minutes post exercise initiation (P less than 0.001). AST and ALT levels were elevated at 60 minutes when compared to baseline. AST levels remained elevated at 240 minutes, unlike ALT levels which returned to baseline values at 240 minutes. Strong physical exercise leads to a significant elevation in blood glutamate, most likely as a result of skeletal muscle damage. 2-ketoglutarate was also found to be elevated for long periods of time, reflecting an ongoing process of glutamate breakdown. Elevated concentrations of AST and ALT in plasma reflect the importance of these enzymes in the maintenance of stable blood glutamate concentrations.

Effect of glutamate and blood glutamate scavengers oxaloacetate and pyruvate on neurological outcome and pathohistology of the hippocampus after traumatic brain injury in rats.

BACKGROUND: Decreasing blood glutamate concentrations after traumatic brain injury accelerates brain-to-blood glutamate efflux, leading to improved neurologic outcomes. The authors hypothesize that treatment with blood glutamate scavengers should reduce neuronal cell loss, whereas administration of glutamate should worsen outcomes. The authors performed histologic studies of neuronal survival in the rat hippocampus after traumatic brain injury and treatment with blood glutamate scavengers. METHODS: Traumatic brain injury was induced on anesthetized male Sprague-Dawley rats by a standardized weight drop. Intravenous treatment groups included saline (control), oxaloacetate, pyruvate, and glutamate. Neurologic outcome was assessed using a Neurological Severity Score at 1 h, and 1, 2, 7, 14, 21, 28 days. Blood glutamate was determined at baseline and 90 min. Four weeks after traumatic brain injury, a histologic analysis of surviving neurons was performed. RESULTS: Oxaloacetate and pyruvate treatment groups demonstrated increased neuronal survival (oxaloacetate 2,200 ± 37, pyruvate 2,108 ± 137 vs. control 1,978 ± 46, P < 0.001, mean ± SD). Glutamate treatment revealed decreased neuronal survival (1,715 ± 48, P < 0.001). Treatment groups demonstrated favorable neurologic outcomes at 24 and 48 h (Neurological Severity Score at 24 and 48 h: 5.5 (1-8.25), 5 (1.75-7.25), P = 0.02 and 3(1-6.5), 4 (1.75-4.5), P = 0.027, median ± corresponding interquartile range). Blood glutamate concentrations were decreased in the oxaloacetate and pyruvate treatment groups. Administration of oxaloacetate and pyruvate was not shown to have any adverse effects. CONCLUSIONS: The authors demonstrate that the blood glutamate scavengers oxaloacetate and pyruvate provide neuroprotection after traumatic brain injury, expressed both by reduced neuronal loss in the hippocampus and improved neurologic outcomes. The findings of this study may bring about new therapeutic possibilities in a variety of clinical settings.

ß2 adrenergic-mediated reduction of blood glutamate levels and improved neurological outcome after traumatic brain injury in rats.

BACKGROUND: Isoflurane-anesthetized rats subjected to traumatic brain injury (TBI) show a transient reduction in blood L-glutamate levels. Having previously observed that isoproterenol produces a sustained decrease in blood glutamate levels in naive rats, we investigated the possible effects of nonselective and selective ß1 and ß2 adrenergic agonists and antagonists both on blood glutamate levels and on the neurological outcomes of rats subjected to TBI. METHODS: Rats received either 10 mL/kg of isotonic saline 1 hour after TBI, 50 µg/kg of isoproterenol pretreatment 30 minutes before TBI, 10 mg/kg of propranolol pretreatment 60 minutes before TBI, 10 mg/kg of metoprolol pretreatment 60 minutes before TBI, or 10 mg/kg of butaxamine pretreatment 40 minutes before TBI and 10 minutes before pretreatment with 50 µg/kg isoproterenol or 10 mg/kg of propranolol 60 minutes after TBI. A neurological severity score (NSS) was measured at 1, 24, and 48 hours after TBI. Blood glutamate, blood glucose, mean arterial blood pressure, and heart rate were measured at the time of drug injection, at the time of TBI, 60 minutes after TBI, and 90 minutes after TBI. RESULTS: Blood glutamate levels decreased spontaneously by 60 minutes after TBI in the control group (P<0.05), reverting to baseline levels by 90 minutes after TBI. A pretreatment with either 10 mg/kg of metoprolol 60 minutes before TBI or with 50 µg/kg of isoproterenol 30 minutes before TBI also reduced blood glutamate levels (P<0.05) both at 90 minutes after TBI and improved the NSS measured 24 and 48 hours after TBI in comparison with the control saline-treated group. However, a 10-mg/kg butoxamine pretreatment 40 minutes before TBI and 10 minutes before pretreatment with 50 µg/kg of isoproterenol or 10 mg/kg of propranolol 60 minutes before TBI neither affected blood glutamate levels across time after TBI nor caused any significant change in the NSS measured 24 and 48 hours after TBI in comparison with the control saline-treated group. A strong correlation (r(2)=0.73) was demonstrated between the percent decrease in blood glutamate levels at 90 minutes after TBI and the percent improvement of NSS measured 24 hours after TBI. CONCLUSIONS: The results suggest that the transient blood glutamate reduction seen after TBI is the result of a stress response and of the activation of the sympathetic nervous system through the ß2 adrenergic receptors, causing an increase of the brain-to-blood efflux of glutamate observed with excess brain glutamate levels after a brain insult. This strongly correlates with the neurological improvement observed 24 hours after TBI.

The effect of hyperthermia on blood glutamate levels.

INTRODUCTION: Glutamate neurotoxicity is determined by the balance between glutamate release within the brain and efflux of excess glutamate from the brain. Brain-to-blood efflux of glutamate is increased by decreasing the concentration of glutamate in blood. Little is known about the effect of hyperthermia on blood glutamate concentrations, and the effectiveness of blood glutamate-decreasing mechanisms in these conditions. Although hyperthermia is hypothesized to decrease blood glutamate concentrations by activation of stress mechanisms, blunting the stress response by blocking ß-adrenergic receptors should prevent this decrease. Furthermore, during hyperthermia there should be a concurrent process of leakage of glutamate from muscle tissue into blood, resulting in a contradictory increase of blood glutamate concentrations. In this study we investigated the effects of hyperthermia on blood glutamate levels and studied the effects of the ß-adrenergic receptor antagonist propranolol on stress-induced changes in glutamate levels. We then studied the effectiveness of the blood glutamate scavenger oxaloacetate on hyperthermia-induced increases of glutamate levels. MATERIALS AND METHODS: Twenty-four rats were randomly divided into 3 groups. Rats' body temperatures were increased (by 1°C every 40 minutes) from 37°C to 42°C. The first group received 1 mL per 100 g of isotonic saline (control). The second group received 1 mL per 100 g of 1M oxaloacetate when the temperature reached 39°C. The third group received 10 mg/kg of propranolol before initiation of the warming. RESULTS: Warming the rats from 37°C to 39°C decreased the blood glutamate levels in the control group (P < 0.01) and oxaloacetate treatment group (P < 0.0001), whereas further increases in temperature from 40°C to 42°C increased the blood glutamate levels (P < 0.01 and P < 0.0001, respectively). Pretreatment with propranolol prevented the decrease in blood glutamate concentrations seen in mild hyperthermia and did not affect the increase in blood glutamate levels seen at temperatures of 41°C and 42°C (P < 0.005). DISCUSSION: The results of this study demonstrated that hyperthermia leads to decreases in glutamate levels in the blood, presumably by activation of the sympathetic nervous system. Oxaloacetate, previously reported to reduce blood glutamate levels at 37°C, was ineffective at temperatures over 40°C. Propranolol pretreatment blunted the initial decrease in blood glutamate, and thereafter had no effect when compared with control and treatment groups. Understanding the mechanisms underlying glutamate regulation in the blood during states of hyperthermia and stress has important clinical implications in treating neurodegenerative conditions.

Regulation of blood L-glutamate levels by stress as a possible brain defense mechanism.

Isoflurane-anesthetized rats submitted to a closed head injury (CHI) display a significant decrease of their blood glutamate levels. Having demonstrated that a decrease of blood L-glutamate (glutamate) causes an increase of the driving force for a spontaneous brain-to-blood glutamate efflux, and consequently affords brain neuroprotection, we investigated here the possible mechanisms which can affect blood glutamate levels. Reasoning that the spontaneous decrease of blood glutamate levels post CHI could be part of a stress response, we observed that the stress involved in tail artery catheterization under isoflurane anesthesia does not affect blood glutamate levels. Investigating in naïve rats the stress effectors, we found that corticotropin-releasing factor (CRF) significantly decreased blood glutamate levels. Pretreatment with antalarmine (a selective type-1 CRF receptor antagonist) occludes the CRF-mediated decrease in blood glutamate levels. In contrast, the adrenocorticotrophic hormone (ACTH) did not affect blood glutamate levels. Investigating the effectors of the sympathetic/adrenomedullary system, we observed that in naïve rats, adrenaline but not noradrenaline decreased blood glutamate levels. Confirming the role of adrenaline, propranolol pretreatment (a non-selective beta-antagonist) prevented the spontaneous decrease of blood glutamate observed post CHI. On the strength of these results, we further observed that isoproterenol (a beta(1/2)-selective adrenoreceptor agonist) produced a marked sustained decrease in blood glutamate levels. These results suggest that stress induces a decrease of blood glutamate levels partly via the activation of peripheral CRF receptors and the activation of the beta-adrenoreceptors. We propose that this newly identified component of the stress response could be a peripherally mediated defense mechanism of the injured brain against the deleterious effects of excess glutamate.

The neuroprotective effects of oxaloacetate in closed head injury in rats is mediated by its blood glutamate scavenging activity: evidence from the use of maleate.

INTRODUCTION: Treatment with oxaloacetate after traumatic brain injury has been shown to decrease blood glutamate levels and protect against the neurotoxic effects of glutamate on the brain. A number of potential mechanisms have been suggested to explain oxaloacetate-induced neuroprotection. We hypothesize that the primary mechanism by which intravenous oxaloacetate provides neuroprotection is by activation of the blood glutamate-scavenging enzyme glutamate-oxaloacetate transaminase, increasing thereby the driving force for the efflux of excess glutamate from brain interstitial fluids into blood. If so, coadministration of maleate, a glutamate-oxaloacetate transaminase-blocker is expected to prevent the neuroprotective effects of oxaloacetate. MATERIALS AND METHODS: A neurological severity score (NSS) was measured 1 hour after closed head injury (CHI) in rats. Then, rats received 30 microL/min/100 g infusion of saline, or 1 mmol/100 g solution of oxaloacetate, maleate, or a mixture of oxaloacetate and maleate. NSS was reassessed at 24 and 48 hour after CHI. Blood glutamate and glucose levels were measured at 0, 60, 90, and 120 minutes. RESULTS: NSS improved significantly at 24 hour (P<0.001) and 48 hour (P<0.001) only in the rats treated with oxaloacetate. Blood glutamate decreased significantly in the oxaloacetate-treated group at 90 minute (at the conclusion of oxaloacetate administration) (P<0.00001), but not in the control, maleate or oxaloacetate+maleate groups. A strong correlation r2=0.86 was found to exist between the percent decrease in blood glutamate levels and percent improvement in NSS. DISCUSSION: The results of this study demonstrate that the primary mechanism by which oxaloacetate provides neuroprotective activity after CHI is related to its blood glutamate scavenging activity. Management of blood glutamate concentration may have important implications in the treatment of acute brain conditions, including CHI and stroke.