Regional Anesthesia Techniques for Shoulder Surgery in High-Risk Pulmonary Patients.

Patients with pre-existing pulmonary conditions are at risk for experiencing perioperative complications and increased morbidity. General anesthesia has historically been used for shoulder surgery, though regional anesthesia techniques are increasingly used to provide anesthesia and improved pain control after surgery. Relative to regional anesthesia, patients who undergo general anesthesia may be more prone to risks of barotrauma, postoperative hypoxemia, and pneumonia. High-risk pulmonary patients, in particular, may be exposed to these risks of general anesthesia. Traditional regional anesthesia techniques for shoulder surgery are associated with high rates of phrenic nerve paralysis which significantly impairs pulmonary function. Newer regional anesthesia techniques have been developed, however, that provide effective analgesia and surgical anesthesia while having much lower rates of phrenic nerve paralysis, thereby preserving pulmonary function.

Patient perceptions of pain management and opioid use prior to hip arthroplasty.

OBJECTIVE: Qualitative assessment investigating patients' perceptions related to opioids including their role in pain control, risks, and handling and disposal prior to undergoing hip replacement. DESIGN: A prospective, cross-sectional survey study. SETTING: Large urban teaching hospital specializing in orthopedic surgery affiliated with Weill Cornell Medical College. PARTICIPANTS: Patients aged 18-80, English-speaking, without recent or chronic opioid use, and planning to undergo primary total hip replacement. A total of 128 patients were enrolled and completed the study. INTERVENTION: A 27-item interview evaluating perceptions on opioid-related -topics. MAIN OUTCOME MEASURES: Responses to interview questions were documented by research assistant. RESULTS: Most patients believe that there should be minimal or no pain with the use of opioids, though they also agree that opioids should be limited to pain that interferes with function or activity. Patients generally appreciate risks of addiction with opioids but are less familiar with risks associated with sleep apnea and sedatives. Minority of patients understand that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in combination with opioids would effectively reduce pain. Majority of patients were unsure of how to properly store and dispose of opioids. CONCLUSIONS: Qualitative assessment demonstrates that patients may benefit from education and discussion specifically about pain expectations, the role of opioids in treating pain, multimodal analgesia, and proper storage and disposal.

Cannabis and Cannabinoids in the Perioperative Period.

Cannabis use is increasingly common, and with a growing number of jurisdictions implementing legalization frameworks, it is likely that providers will encounter more patients who use cannabis. Therefore, it is important for providers to understand the implications of cannabis use and practical considerations for the perioperative period. Cannabis affects multiple organ systems and may influence intraoperative anesthesia, as well as postoperative pain management. The effects of cannabis and key anesthetic considerations are reviewed here.

Effectiveness of Perioperative Opioid Educational Initiatives: A Systematic Review and Meta-Analysis.

BACKGROUND: Opioids are the most commonly prescribed analgesics in the United States. Current guidelines have proposed education initiatives to reduce the risk of chronic opioid consumption, yet there is lack of efficacy data on such interventions. Our study evaluates the impact of perioperative opioid education on postoperative opioid consumption patterns including opioid cessation, number of pills consumed, and opioid prescription refills. METHODS: The MEDLINE/PubMed, Embase, Cochrane Library, Scopus, and Google Scholar databases were systematically searched for randomized controlled trials (RCTs) assessing the impact of perioperative educational interventions (using either paper- or video-based instruments regarding pain management and drug-induced side effects) on postoperative opioid patterns compared to standard preoperative care among patients undergoing elective surgery. Our end points were opioid consumption (number of pills used), appropriate disposal of unused opioids, opioid cessation (defined as no use of opioids), and opioid refills within 15 days, 6 weeks, and 3 months. RESULTS: In total, 11 RCTs fulfilled the inclusion criteria, totaling 1604 patients (804 received opioid education, while 800 received standard care). Six trials followed patients for 15 days after surgery, and 5 trials followed patients up to 3 months. After 15 days, the opioid education group consumed a lower number of opioid pills than those in the control group (weighted mean difference [WMD], -3.39 pills; 95% confidence interval [CI], -6.40 to -0.37; P =.03; I2 = 69%) with no significant difference in overall opioid cessation (odds ratio [OR], 0.25; 95% CI, 0.04-1.56; P = .14; I2 = 83%). Likewise, perioperative opioid education did not have significant effects on opioid cessation at 6 weeks (OR, 0.69; 95% CI, 0.45-1.05; P = .10; I2 = 0%) and 3 months (OR, 0.59; 95% CI,0.17-2.01; P = .10; I2 = 0%) after surgery, neither reduced the need for opioid refills at 15 days (OR, 0.57; 95% CI, 0.28-1.15; P = .12; I2 = 20%) and 6 weeks (OR, 1.08; 95% CI, 0.59-1.98; P = .80; I2 = 37%). There was no statistically significant difference in the rate of appropriate disposal of unused opioids between both groups (OR, 1.99; 95% CI, 0.66-6.00; P = .22; I2 = 71%). Subgroup analysis by type of educational intervention showed a statistical reduction of opioid consumption at 15 days when implementing multimedia/audiovisual strategies (4 trials: WMD, -4.05 pills; 95% CI, -6.59 to -1.50; P = .002; I2 = 45%), but there was no apparent decrease when using only paper-based strategies (2 trials: WMD, -2.31 pills; 95% CI, -12.21 to 7.59; P = .65; I2 = 80%). CONCLUSIONS: Perioperative educational interventions reduced the number of opioid pills consumed at 15 days but did not demonstrate a significant effect on opioid cessation or opioid refills at 15 days, 6 weeks, and 3 months. Further randomized trials should focus on evidence-based educational interventions with strict homogeneity of material to draw a more definitive recommendation.

Peripheral nerve block anesthesia/analgesia for patients undergoing primary hip and knee arthroplasty: recommendations from the International Consensus on Anesthesia-Related Outcomes after Surgery (ICAROS) group based on a systematic review and meta-analysis of current literature.

BACKGROUND: Evidence-based international expert consensus regarding the impact of peripheral nerve block (PNB) use in total hip/knee arthroplasty surgery. METHODS: A systematic review and meta-analysis: randomized controlled and observational studies investigating the impact of PNB utilization on major complications, including mortality, cardiac, pulmonary, gastrointestinal, renal, thromboembolic, neurologic, infectious, and bleeding complications.Medline, PubMed, Embase, and Cochrane Library including Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, were queried from 1946 to August 4, 2020.The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess evidence quality and for the development of recommendations. RESULTS: Analysis of 122 studies revealed that PNB use (compared with no use) was associated with lower ORs for (OR with 95% CIs) for numerous complications (total hip and knee arthroplasties (THA/TKA), respectively): cognitive dysfunction (OR 0.30, 95% CI 0.17 to 0.53/OR 0.52, 95% CI 0.34 to 0.80), respiratory failure (OR 0.36, 95% CI 0.17 to 0.74/OR 0.37, 95% CI 0.18 to 0.75), cardiac complications (OR 0.84, 95% CI 0.76 to 0.93/OR 0.83, 95% CI 0.79 to 0.86), surgical site infections (OR 0.55 95% CI 0.47 to 0.64/OR 0.86 95% CI 0.80 to 0.91), thromboembolism (OR 0.74, 95% CI 0.58 to 0.96/OR 0.90, 95% CI 0.84 to 0.96) and blood transfusion (OR 0.84, 95% CI 0.83 to 0.86/OR 0.91, 95% CI 0.90 to 0.92). CONCLUSIONS: Based on the current body of evidence, the consensus group recommends PNB use in THA/TKA for improved outcomes. RECOMMENDATION: PNB use is recommended for patients undergoing THA and TKA except when contraindications preclude their use. Furthermore, the alignment of provider skills and practice location resources needs to be ensured. Evidence level: moderate; recommendation: strong.

A Comprehensive Enhanced Recovery Pathway for Rotator Cuff Surgery Reduces Pain, Opioid Use, and Side Effects.

BACKGROUND: Patients often have moderate to severe pain after rotator cuff surgery, despite receiving analgesics and nerve blocks. There are many suggested ways to improve pain after rotator cuff surgery, but the effects of adopting a pathway that includes formal patient education, a long-acting nerve block, and extensive multimodal analgesia are unclear. QUESTIONS/PURPOSES: (1) Does adoption of a clinical pathway incorporating patient education, a long-acting nerve block, and preemptive multimodal analgesia reduce the worst pain during the first 48 hours after surgery compared with current standard institutional practices? (2) Does adoption of the pathway reduce opioid use? (3) Does adoption of the pathway reduce side effects and improve patient-oriented outcomes? METHODS: From September 2018 to January 2020, 281 patients scheduled for arthroscopic ambulatory rotator cuff surgery were identified for this paired sequential prospective cohort study. Among patients in the control group, 177 were identified, 33% (58) were not eligible, for 11% (20) staff was not available, 56% (99) were approached, 16% (29) declined, 40% (70) enrolled, and 40% (70) were analyzed (2% [4] lost to follow-up for secondary outcomes after postoperative day 2). For patients in the pathway cohort, 104 were identified, 17% (18) were not eligible, for 11% (11) staff was not available, 72% (75) were approached, 5% (5) declined, 67% (70) enrolled, and 67% (70) were analyzed (3% [3] lost to follow-up for secondary outcomes after postoperative day 2). No patients were lost to follow-up for primary outcome; for secondary outcomes, four were lost in the control group and three in the pathway group after postoperative day 2 (p = 0.70). The initial 70 patients enrolled received routine care (control group), and in a subsequent cohort, 70 patients received care guided by a pathway (pathway group). Of the 205 eligible patients, 68% (140) were included in the analysis. This was not a study comparing two tightly defined protocols but rather a study to determine whether adoption of a pathway would alter patient outcomes. For this reason, we used a pragmatic (real-world) study design that did not specify how control patients would be treated, and it did not require that all pathway patients receive all components of the pathway. We developed the pathway in coordination with a group of surgeons and anesthesiologists who agreed to apply the pathway as much as was viewed practical for each individual patient. Patients in both groups received a brachial plexus nerve block with sedation. Major differences between the pathway and control groups were: detailed patient education regarding reasonable pain expectations with a goal of reducing opioid use (no formal educational presentation was given to the control), a long-acting nerve block using bupivacaine with dexamethasone (control patients often received shorter-acting local anesthetic without perineural dexamethasone), and preemptive multimodal analgesia including intraoperative ketamine, postoperative acetaminophen, NSAIDs, and gabapentin at bedtime, with opioids as needed (control patients received postoperative opioids but most did not get postoperative NSAIDS and no controls received gabapentin or separate prescriptions for acetaminophen). The primary outcome was the numerical rating scale (NRS) worst pain with movement 0 to 48 hours after block placement. The NRS pain score ranges from 0 (no pain) to 10 (worst pain possible). The minimum clinically important difference (MCID) [12] for NRS that was used for calculation of the study sample size was 1.3 [18], although some authors suggest 1 [13] or 2 [5] are appropriate; if we had used an MCID of 2, the sample size would have been smaller. Secondary outcomes included NRS pain scores at rest, daily opioid use (postoperative day 1, 2, 7, 14), block duration, patient-oriented pain questions (postoperative day 1, 2, 7, 14), and patient and physician adherence to pathway. RESULTS: On postoperative day 1, pathway patients had lower worst pain with movement (3.3 ± 3.1) compared with control patients (5.6 ± 3.0, mean difference -2.7 [95% CI -3.7 to -1.7]; p < 0.001); lower scores were also seen for pain at rest (1.9 ± 2.3 versus 4.0 ± 2.9, mean difference -2.0 [95% CI -2.8 to -1.3]; p < 0.001). Cumulative postoperative opioid use (0-48 hours) was reduced (pathway oral morphine equivalent use was 23 ± 28 mg versus 44 ± 35 mg, mean difference 21 [95% CI 10 to 32]; p < 0.01). The greatest difference in opioid use was in the first 24 hours after surgery (pathway 7 ± 12 mg versus control 21 ± 21 mg, mean difference -14 [95% CI -19 to -10]; p < 0.01). On postoperative day 1, pathway patients had less interference with staying asleep compared with control patients (0.5 ± 1.6 versus 2.6 ± 3.3, mean difference -2.2 [95% CI -3.3 to -1.1]; p < 0.001); lower scores were also seen for interference with activities (0.9 ± 2.3 versus 1.9 ± 2.9, mean difference -1.1 [95% CI -2 to -0.1]; p = 0.03). Satisfaction with pain treatment on postoperative day 1 was higher among pathway patients compared with control patients (9.2 ± 1.7 versus 8.2 ± 2.5, mean difference 1.0 [95% CI 0.3 to 1.8]; p < 0.001). On postoperative day 2, pathway patients had lower nausea scores compared with control patients (0.3 ± 1.1 versus 1 ± 2.1, mean difference -0.7 [95% CI -1.2 to -0.1]; p = 0.02); lower scores were also seen for drowsiness on postoperative day 1 (1.7 ± 2.7 versus 2.6 ± 2.6, mean difference -0.9 [95% CI - 1.7 to -0.1]; p = 0.03). CONCLUSION: Adoption of the pathway was associated with improvement in the primary outcome (pain with movement) that exceeded the MCID. Patients in the pathway group had improved patient-oriented outcomes and fewer side effects. This pathway uses multiple analgesic drugs, which may pose risks to elderly patients, in particular. Therefore, in evaluating whether to use this pathway, clinicians should weigh the effect sizes against the potential risks that may emerge with large scale use, consider the difficulties involved in adapting a pathway to local practice so that pathway will persist, and recognize that this study only enrolled patients among surgeons and the anesthesiologists that advocated for the pathway; results may have been different with less enthusiastic clinicians. This pathway, based on a long-lasting nerve block, multimodal analgesia, and patient education can be considered for adoption. LEVEL OF EVIDENCE: Level II, therapeutic study.

Anesthesia-induced Recognition Deficit Is Improved in Postnatally Gonadectomized Male Rats.

BACKGROUND: Preclinical investigations of the effects of general anesthesia on the young brain show differences in vulnerability of males and females to anesthetic exposure at different times during development. However, the mechanism underlying this sex difference is poorly understood. Perinatal testosterone is the primary determinant of sexual differentiation and likely plays an important role in defining the period of susceptibility to anesthetic injury. We investigated whether the removal of testosterone through gonadectomy shortly after birth would improve cognitive outcomes in male rodents after early anesthesia exposure. METHODS: Male Sprague Dawley rats underwent gonadectomy at postnatal day 2 (P2), followed by exposure to 6 hours of isoflurane at P7. A control cohort of gonad-intact male littermates was simultaneously exposed. All rats were subjected to a series of object recognition and association tasks beginning at P42. Cell death in the thalamus and hippocampus was assessed in a separate cohort. RESULTS: All groups performed similarly on the Novel Object Recognition task; however, the gonad-intact isoflurane group exhibited decreased performance in the more difficult tasks. This deficit was ameliorated in the gonadectomized group. Cell death was similar between both isoflurane-exposed groups, regardless of gonadectomy. CONCLUSIONS: The absence of testosterone does not block cell death after anesthesia in specific brain regions of interest; however, does provide some neuroprotection as evidenced by the improved cognitive test performance during adulthood. These findings suggest that testosterone may be mechanistically involved in the sex-specific effects of anesthetic injury on the developing brain by extending the vulnerable period in male rats.

Educating Patients Regarding Pain Management and Safe Opioid Use After Surgery: A Narrative Review.

In recent years, there have been escalating concerns related to the opioid epidemic. With a steadily increasing opioid supply, it is critical to provide proper education to patients who are prescribed these medications. Education should be emphasized as a means of ensuring safe use and potentially as a strategy for curbing the opioid supply. Patients who undergo surgery are frequently prescribed opioids for postoperative pain; however, the content and delivery of information related to usage is inconsistent and often inadequate. Lack of education on postoperative pain management and opioid use places patients at risk for poor compliance and worse pain control. Furthermore, patients are often not properly educated on opioid-related side effects and risks or about safe behaviors when taking medications. The majority of patients are also not informed about how to store and dispose of leftover medications. Patients who are prescribed opioids require education preoperatively to cover the topics of pain management, opioid-related side effects, and risks, storage, and disposal. Evidence from various studies demonstrates that educational interventions improve knowledge and potentially lead to safer behaviors and reduced opioid use. Education can be provided in various formats with each having unique advantages and limitations.

Anaesthetic care of patients undergoing primary hip and knee arthroplasty: consensus recommendations from the International Consensus on Anaesthesia-Related Outcomes after Surgery group (ICAROS) based on a systematic review and meta-analysis.

BACKGROUND: Evidence-based international expert consensus regarding anaesthetic practice in hip/knee arthroplasty surgery is needed for improved healthcare outcomes. METHODS: The International Consensus on Anaesthesia-Related Outcomes after Surgery group (ICAROS) systematic review, including randomised controlled and observational studies comparing neuraxial to general anaesthesia regarding major complications, including mortality, cardiac, pulmonary, gastrointestinal, renal, genitourinary, thromboembolic, neurological, infectious, and bleeding complications. Medline, PubMed, Embase, and Cochrane Library including Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, from 1946 to May 17, 2018 were queried. Meta-analysis and Grading of Recommendations Assessment, Development and Evaluation approach was utilised to assess evidence quality and to develop recommendations. RESULTS: The analysis of 94 studies revealed that neuraxial anaesthesia was associated with lower odds or no difference in virtually all reported complications, except for urinary retention. Excerpt of complications for neuraxial vs general anaesthesia in hip/knee arthroplasty, respectively: mortality odds ratio (OR): 0.67, 95% confidence interval (CI): 0.57-0.80/OR: 0.83, 95% CI: 0.60-1.15; pulmonary OR: 0.65, 95% CI: 0.52-0.80/OR: 0.69, 95% CI: 0.58-0.81; acute renal failure OR: 0.69, 95% CI: 0.59-0.81/OR: 0.73, 95% CI: 0.65-0.82; deep venous thrombosis OR: 0.52, 95% CI: 0.42-0.65/OR: 0.77, 95% CI: 0.64-0.93; infections OR: 0.73, 95% CI: 0.67-0.79/OR: 0.80, 95% CI: 0.76-0.85; and blood transfusion OR: 0.85, 95% CI: 0.82-0.89/OR: 0.84, 95% CI: 0.82-0.87. CONCLUSIONS: Recommendation: primary neuraxial anaesthesia is preferred for knee arthroplasty, given several positive postoperative outcome benefits; evidence level: low, weak recommendation. RECOMMENDATION: neuraxial anaesthesia is recommended for hip arthroplasty given associated outcome benefits; evidence level: moderate-low, strong recommendation. Based on current evidence, the consensus group recommends neuraxial over general anaesthesia for hip/knee arthroplasty. TRIAL REGISTRY NUMBER: PROSPERO CRD42018099935.

The prescription opioid crisis: role of the anaesthesiologist in reducing opioid use and misuse.

Reports of strategies to prevent and treat the opioid epidemic are growing. Significant attention has been paid to the benefits of opioid addiction research, clinical prescribing, and public policy initiatives in curbing the epidemic. However, the role of the anaesthesiologist in minimising opioid use and misuse remains underexplored. For many patients with an opioid use disorder, the perioperative period represents the source of initial exposure. As perioperative physicians, anaesthesiologists are in the unique position to manage pain effectively while simultaneously decreasing opioid consumption. Multiple opportunities exist for anaesthesiologists to minimise opioid exposure and prevent subsequent persistent opioid use. We present a global strategy for decreasing perioperative opioid use and misuse among surgical patients. A historical perspective of the opioid epidemic is presented, together with an analysis of opioid supply and demand forces. We then present specific temporal strategies for opioid use reduction in the perioperative period. We emphasise the importance of preoperative identification of patients at risk for long-term opioid use and misuse, review the evidence supporting the opioid sparing capacity of individual multimodal analgesic agents, and discuss the benefits of regional anaesthesia for minimising opioid consumption. We describe postoperative and post-discharge tools, including effective multimodal analgesia and the role of a transitional pain service. Finally, we offer general institutional strategies that can be led by anaesthesiologists, identify gaps in knowledge, and offer directions for future research.

Use of test dose allows early detection of subdural local anesthetic injection with lumbar plexus block.

A 56year-old woman underwent a lumbar plexus block for a revision of a left total hip arthroplasty. During the block procedure, the needle was advanced over the transverse process and isolated quadriceps twitches were elicited. After administering a test dose of 3ml of 1.5% lidocaine, the patient developed loss of sensation in the L3-4 dermatomal distribution that progressed caudally to involve both legs followed by inability to move the left leg. The patient shortly thereafter became hypotensive and sensory block spread cephalad and peaked at C7 bilaterally suggesting possible subdural spread of local anesthetic. The patient was resuscitated with normalization of blood pressure and eventually had full resolution of motor and sensory block. Subdural spread of local anesthetic is a potential complication of lumbar plexus block related perhaps to injection of local anesthetic near dural sleeves of nerve roots. The use of a test dose allows early recognition of subdural injection and may limit consequences of inadvertent subdural spread of local anesthetic.

Pneumothorax after tracheostomy closure with successful nonsurgical management.

A 3-year-old girl presented for routine closure of her tracheostomy site. She was intubated easily for the procedure, and the wound was closed with a drain in place. In recovery, the mother noticed fullness in the patient's submandibular region, and on examination, the girl had subcutaneous emphysema in the neck bilaterally. She returned to the operating room for exploration, and air was released from the surgical site. The wound was again closed with a drain in place, and the patient was extubated uneventfully. After arriving to the pediatric intensive care unit for monitoring, the patient acutely developed respiratory distress and was found to have pneumomediastinum and pneumothorax and was emergently intubated. She was observed closely, and the following day, the pneumothorax improved, and she successfully extubated without further complication.

Early exposure to volatile anesthetics impairs long-term associative learning and recognition memory.

BACKGROUND: Anesthetic exposure early in life affects neural development and long-term cognitive function, but our understanding of the types of memory that are altered is incomplete. Specific cognitive tests in rodents that isolate different memory processes provide a useful approach for gaining insight into this issue. METHODS: Postnatal day 7 (P7) rats were exposed to either desflurane or isoflurane at 1 Minimum Alveolar Concentration for 4 h. Acute neuronal death was assessed 12 h later in the thalamus, CA1-3 regions of hippocampus, and dentate gyrus. In separate behavioral experiments, beginning at P48, subjects were evaluated in a series of object recognition tests relying on associative learning, as well as social recognition. RESULTS: Exposure to either anesthetic led to a significant increase in neuroapoptosis in each brain region. The extent of neuronal death did not differ between groups. Subjects were unaffected in simple tasks of novel object and object-location recognition. However, anesthetized animals from both groups were impaired in allocentric object-location memory and a more complex task requiring subjects to associate an object with its location and contextual setting. Isoflurane exposure led to additional impairment in object-context association and social memory. CONCLUSION: Isoflurane and desflurane exposure during development result in deficits in tasks relying on associative learning and recognition memory. Isoflurane may potentially cause worse impairment than desflurane.

Effect of combining anesthetics in neonates on long-term cognitive function.

BACKGROUND: With growing evidence that anesthesia exposure in infancy affects cognitive development, it is important to understand how distinct anesthetic agents and combinations can alter long-term memory. Investigations of neuronal death suggest that combining anesthetic agents increases the extent of neuronal injury. However, it is unclear how the use of simultaneously combined anesthetics affects cognitive outcome relative to the use of a single agent. METHODS: Postnatal day 7 (P7) male rats were administered either sevoflurane as a single agent or the combined delivery of sevoflurane with nitrous oxide at 1 Minimum Alveolar Concentration for 4 h. Behavior was assessed in adulthood using the forced alternating T-maze, social recognition, and context-specific object recognition tasks. RESULTS: Animals exposed to either anesthetic were unimpaired in the forced alternating T-maze test and had intact social recognition. Subjects treated with the combined anesthetic displayed a deficit, however, in the object recognition task, while those treated with sevoflurane alone were unaffected. CONCLUSION: A combined sevoflurane and nitrous oxide anesthetic led to a distinct behavioral outcome compared with sevoflurane alone, suggesting that the simultaneous use of multiple agents may uniquely influence early neural and cognitive development and potentially impacts associative memory.

Effect of general anesthesia in infancy on long-term recognition memory in humans and rats.

Anesthesia in infancy impairs performance in recognition memory tasks in mammalian animals, but it is unknown if this occurs in humans. Successful recognition can be based on stimulus familiarity or recollection of event details. Several brain structures involved in recollection are affected by anesthesia-induced neurodegeneration in animals. Therefore, we hypothesized that anesthesia in infancy impairs recollection later in life in humans and rats. Twenty eight children ages 6-11 who had undergone a procedure requiring general anesthesia before age 1 were compared with 28 age- and gender-matched children who had not undergone anesthesia. Recollection and familiarity were assessed in an object recognition memory test using receiver operator characteristic analysis. In addition, IQ and Child Behavior Checklist scores were assessed. In parallel, thirty three 7-day-old rats were randomized to receive anesthesia or sham anesthesia. Over 10 months, recollection and familiarity were assessed using an odor recognition test. We found that anesthetized children had significantly lower recollection scores and were impaired at recollecting associative information compared with controls. Familiarity, IQ, and Child Behavior Checklist scores were not different between groups. In rats, anesthetized subjects had significantly lower recollection scores than controls while familiarity was unaffected. Rats that had undergone tissue injury during anesthesia had similar recollection indices as rats that had been anesthetized without tissue injury. These findings suggest that general anesthesia in infancy impairs recollection later in life in humans and rats. In rats, this effect is independent of underlying disease or tissue injury.

Isoflurane exposure in newborn rats induces long-term cognitive dysfunction in males but not females.

Volatile anesthetics are used widely for achieving a state of unconsciousness, yet these agents are incompletely understood in their mechanisms of action and effects on neural development. There is mounting evidence that children exposed to anesthetic agents sustain lasting effects on learning and memory. The explanation for these behavioral changes remains elusive, although acute neuronal death after anesthesia is commonly believed to be a principal cause. Rodent models have shown that isoflurane exposure in newborns induces acute neuroapoptosis and long-term cognitive impairment. However, the assessment of predisposing factors is lacking. We investigated the role of sex by delivering isoflurane to postnatal day (P)7 male and female Sprague Dawley rats for 4 h. Brain cell death was assessed 12 h later using FluoroJade C staining in the thalamus, CA1-3 regions of hippocampus, and dentate gyrus. Behavior was assessed separately using a series of object recognition tasks and a test of social memory beginning at P38. We found that isoflurane exposure significantly increased neuronal death in each brain region with no difference between sexes. Behavioral outcome was also equivalent in simple novel object recognition. However, only males were impaired in the recognition of objects in different locations and contexts. Males also exhibited deficient social memory while females were intact. The profound behavioral impairment in males relative to females, in spite of comparable cell death, suggests that males are more susceptible to long-term cognitive effects and this outcome may not be exclusively attributed to neuronal death.