Immunomodulatory and pro-oncologic effects of ketamine and isoflurane anesthetics in a murine model.

INTRODUCTION: Volatile and intravenous anesthetics may worsen oncologic outcomes in basic science animal models. These effects may be related to suppressed innate and adaptive immunity, decreased immunosurveillance, and disrupted cellular signaling. We hypothesized that anesthetics would promote lung tumor growth via altered immune function in a murine model and tested this using an immunological control group of immunodeficient mice. METHODS: Lewis lung carcinoma cells were injected via tail vein into C57BL/6 immunocompetent and NSG immunodeficient mice during exposure to isoflurane and ketamine versus controls without anesthesia. Mice were imaged on days 0, 3, 10, and 14 post-tumor cell injection. On day 14, mice were euthanized and organs fixed for metastasis quantification and immunohistochemistry staining. We compared growth of tumors measured from bioluminescent imaging and tumor metastasis in ex vivo bioluminescent imaging of lung and liver. RESULTS: Metastases were significantly greater for immunocompromised NSG mice than immunocompetent C57BL/6 mice over the 14-day experiment (partial η2 = 0.67, 95% CI = 0.54, 0.76). Among immunocompetent mice, metastases were greatest for mice receiving ketamine, intermediate for those receiving isoflurane, and least for control mice (partial η2 = 0.88, 95% CI = 0.82, 0.91). In immunocompetent mice, significantly decreased T lymphocyte (partial η2 = 0.83, 95% CI = 0.29, 0.93) and monocyte (partial η2 = 0.90, 95% CI = 0.52, 0.96) infiltration was observed in anesthetic-treated mice versus controls. CONCLUSIONS: The immune system appears central to the pro-metastatic effects of isoflurane and ketamine in a murine model, with decreased T lymphocytes and monocytes likely playing a role.

Cancer Immunotherapies: What the Perioperative Physician Needs to Know.

PURPOSE OF REVIEW: For patients with cancer, treatment may include combination therapy, including surgery and immunotherapy. Here, we review perioperative considerations for the patient prescribed immunotherapeutic agents. RECENT FINDINGS: The perioperative period is a poignant moment in the journey of a patient with cancer, potentially deemed most influential compared to other moments in the care continuum. Several immunotherapeutic medications have been employed near the time of surgery to potentially increase effectiveness. Of the various drug classes, including immune checkpoint inhibitors, cytokines, toll-like receptor agonists, and oncolytic viruses, among others, several notable immune-related adverse effects were noted. They range from minor effects to more serious ones, such as renal failure, myocarditis, and tumor growth. Surgery and immunotherapy are often employed in combination for primary treatment and prevention of cancer recurrence. Careful review and consideration of the pharmacokinetics, pharmacodynamics, and toxicities of immunotherapy benefit the perioperative physician and their patients.

A Retrospective Analysis of Patients Undergoing Telemedicine Evaluation in the PreAnesthesia Testing Clinic at H. Lee Moffitt Cancer Center.

BACKGROUND: Telemedicine for preanesthesia evaluation can decrease access disparities by minimizing commuting, time off work, and lifestyle disruptions from frequent medical visits. We report our experience with the first 120 patients undergoing telemedicine preanesthesia evaluation at Moffitt Cancer Center. METHODS: This is a retrospective analysis of 120 patients seen via telemedicine for preanesthesia evaluation compared with an in-person cohort meeting telemedicine criteria had it been available. Telemedicine was conducted from our clinic to a patient's remote location using video conferencing. Clinic criteria were revised to create a tier of eligible patients based on published guidelines and anesthesiologist consensus. RESULTS: Day-of-surgery cancellation rate was 1.67% in the telemedicine versus 0% in the in-person cohort. The two telemedicine group cancellations were unrelated to medical workup, and cancellation rate between the groups was not statistically significant (P = .49). Median round trip distance and time saved by the telemedicine group was 80 miles [range 4; 1180] and 121 minutes [range 16; 1034]. Using the federal mileage rate, the median cost savings was $46 [range $2.30; 678.50] per patient. Patients were similar in gender and race in both groups (P = .23 and .75, respectively), but the in-person cohort was older and had higher American Society of Anesthesiologists physical status classification (P = .0003). CONCLUSIONS: Telemedicine preanesthesia evaluation results in time, distance, and financial savings without increased day-of-surgery cancellations. This is useful in cancer patients who travel significant distances to specialty centers and have a high frequency of health care visits. American Society of Anesthesiologists Physical Status classification and age differences between cohorts indicate possible patient or provider selection bias. Randomized controlled trials will aid in further exploring this technology.

The Effects of Anesthetics and Perioperative Medications on Immune Function: A Narrative Review.

Preclinical and clinical studies have sought to better understand the effect of anesthetic agents, both volatile and intravenous, and perioperative adjuvant medications on immune function. The immune system has evolved to incorporate both innate and adaptive components, which are delicately interwoven and essential for host defense from pathogens and malignancy. This review summarizes the complex and nuanced relationship that exists between each anesthetic agent or perioperative adjuvant medication studied and innate and adaptive immune function with resultant clinical implications. The most commonly used anesthetic agents were chosen for review including volatile agents (sevoflurane, isoflurane, desflurane, and halothane), intravenous agents (propofol, ketamine, etomidate, and dexmedetomidine), and perioperative adjuvant medications (benzodiazepines, opioids, nonsteroidal anti-inflammatory drugs [NSAIDs], and local anesthetic agents). Patients who undergo surgery experience varying combinations of the aforementioned anesthetic agents and adjuncts, depending on the type of surgery and their comorbidities. Each has unique effects on immunity, which may be more or less ideal depending on the clinical situation. Further study is needed to better understand the clinical effects of these relationships so that patient-specific strategies can be developed to improve surgical outcomes.

Rupture of an epidural filter connector during bolus administration of local anesthetic: a case report.

BACKGROUND: Epidural catheters are routinely placed for many surgical procedures and to treat various pain conditions. Known complications arising from epidural catheter equipment malfunction include epidural pump failure, epidural catheter shearing, epidural catheter connector failure, epidural filter connector cracking, and loss-of-resistance syringe malfunction. Practitioners need to be aware of these potentially dangerous complications and take measures to mitigate the chances of causing significant patient harm. We report on the complete breakage of an epidural filter connector during epidural bolus administration of local anesthetic by hand with a syringe. CASE PRESENTATION: A B. Braun Perifix® epidural catheter was placed in a 73-year-old male scheduled for radical prostatectomy. During the operation, a continuous infusion of local anesthetic was administered through the epidural catheter in addition to general endotracheal anesthesia. At the conclusion of surgery and after extubation, the patient endorsed incisional pain. The epidural filter connector broke in half as a bolus of local anesthetic was administered by hand with a syringe. The local anesthetic sprayed widely throughout the room as the fragmented epidural filter connector became a projectile object that recoiled and struck the patient. CONCLUSIONS: This incident placed the patient and surrounding healthcare providers at substantial risk for injury and infection from the fractured epidural filter connector becoming a projectile object and from the local anesthetic spray. The most plausible cause of this event was from a large amount of pressure being applied to the filter connector. This may have occurred by excessive force being applied by hand to the syringe, by the presence of a clogged filter, or by the catheter being kinked or blocked proximal to the filter. Being aware of this deleterious complication and potentially modifying existing epidural bolus techniques, such as using smaller syringes with less applied force and checking all epidural components vigilantly prior to and during bolus administration, can help anesthesia providers deliver the safest possible care to patients with epidural catheters.

Intraoperative Hypotension in a Patient with Antithrombin Deficiency, Bilateral Pulmonary Emboli, and Cefazolin Allergy.

In medicine, the search for a clear answer can at times be elusive. However, this does not necessarily preclude the administration of intelligent and thoughtful therapeutic treatments. Here, we describe a complicated emergent event of severe hypotension and near-arrest that occurred in the operating room in a young, healthy woman undergoing outpatient thyroid surgery. We detail the situation as it presented in the operating room and the measures taken to rule out potential life-threatening diagnoses and develop a thoughtful treatment plan. We further describe the evidence for and against the two remaining diagnostic possibilities: anaphylaxis versus acute pulmonary embolism.

Use of a Low Concentration, High Volume Erector Spinae Plane Block for Rescue Analgesia After Melanoma Resection and Axillary Sentinel Lymph Node Biopsy.

The erector spinae plane block (ESPB), a recent innovation in regional anesthesia, has been used for analgesia of the thorax and chest. The case presented describes the use of an ESPB postoperatively for rescue analgesia on an elderly, opioid-naïve patient, who had severe postoperative pain after outpatient surgery at an axillary sentinel lymph node biopsy site refractory to escalating IV opioid doses. The rescue ESPB was successful in reducing the patient's pain to 0/10, allowing the patient to be discharged home and preventing a costly hospital admission.

The Intersection of Regional Anesthesia and Cancer Progression: A Theoretical Framework.

The surgical stress and inflammatory response and volatile anesthetic agents have been shown to promote tumor metastasis in animal and in-vitro studies. Regional neuraxial anesthesia protects against these effects by decreasing the surgical stress and inflammatory response and associated changes in immune function in animals. However, evidence of a similar effect in humans remains equivocal due to the high variability and retrospective nature of clinical studies and difficulty in directly comparing regional versus general anesthesia in humans. We propose a theoretical framework to address the question of regional anesthesia as protective against metastasis.This theoretical construct views the immune system, circulating tumor cells, micrometastases, and inflammatory mediators as distinct populations in a highly connected system. In ecological theory, highly connected populations demonstrate more resilience to local perturbations but are prone to system-wide shifts compared with their poorly connected counterparts. Neuraxial anesthesia transforms the otherwise system-wide perturbations of the surgical stress and inflammatory response and volatile anesthesia into a comparatively local perturbation to which the system is more resilient. We propose this framework for experimental and mathematical models to help determine the impact of anesthetic choice on recurrence and metastasis and create therapeutic strategies to improve cancer outcomes after surgery.

Placement of a Double-Lumen Endotracheal Tube Using a Combined Bronchoscopy and Fluoroscopy Technique: A Case Report.

Bronchial artery embolization (BAE) is a well-established intervention for hemoptysis that requires airway management by a trained anesthesiologist. The use of fluoroscopic guidance for positioning a double-lumen endotracheal tube (DLT) has been described in previous studies. The case presented illustrates a combined fluoroscopic- and bronchoscopic-guided approach for positioning a DLT in a patient with active pulmonary hemorrhage causing obstruction of views on bronchoscopy. This combined technique proved valuable in a situation marked by high clinical urgency.

Disrupted sleep and delayed recovery from chronic peripheral neuropathy are distinct phenotypes in a rat model of metabolic syndrome.

BACKGROUND: Sleep apnea, hypertension, atherosclerosis, and obesity are features of metabolic syndrome associated with decreased restorative sleep and increased pain. These traits are relevant for anesthesiology because they confer increased risks of a negative anesthetic outcome. This study tested the one-tailed hypothesis that rats bred for low intrinsic aerobic capacity have enhanced nociception and disordered sleep. METHODS: Rats were developed from a breeding strategy that selected for low aerobic capacity runners (LCR) and high aerobic capacity runners (HCR). Four phenotypes were quantified. Rats underwent von Frey sensory testing (n = 12), thermal nociceptive testing (n = 12), electrographic recordings of sleep and wakefulness (n = 16), and thermal nociceptive testing (n = 14) before and for 6 weeks after a unilateral chronic neuropathy of the sciatic nerve. RESULTS: Paw withdrawal latency to a thermal nociceptive stimulus was significantly (P < 0.01) lower in LCR than HCR rats. There were also significant differences in sleep, with LCR rats spending significantly (P < 0.01) more time awake (18%) and less time in nonrapid eye movement sleep (-19%) than HCR rats. Nonrapid eye movement sleep episodes were of shorter duration (-34%) in LCR than HCR rats. Rapid eye movement sleep of LCR rats was significantly more fragmented than rapid eye movement sleep of HCR rats. LCR rats required 2 weeks longer than HCR rats to recover from peripheral neuropathy. CONCLUSIONS: Rodents with low aerobic capacity exhibit features homologous to human metabolic syndrome. This rodent model offers a novel tool for characterizing the mechanisms through which low aerobic function and obesity might confer increased risks for anesthesia.