Effects of Subnormothermic Regulated Hepatic Reperfusion on Mitochondrial and Transcriptomic Profiles in a Porcine Model.

OBJECTIVE: We sought to investigate the biological effects of pre-reperfusion treatments of the liver after warm and cold ischemic injuries in a porcine donation after circulatory death model. SUMMARY OF BACKGROUND DATA: Donation after circulatory death represents a severe form of liver ischemia and reperfusion injury that has a profound impact on graft function after liver transplantation. METHODS: Twenty donor pig livers underwent 60 minutes of in situ warm ischemia after circulatory arrest and 120 minutes of cold static preservation prior to simulated transplantation using an ex vivo perfusion machine. Four reperfusion treatments were compared: Control-Normothermic (N), Control- Subnormothermic (S), regulated hepatic reperfusion (RHR)-N, and RHR-S (n = 5 each). The biochemical, metabolic, and transcriptomic profiles, as well as mitochondrial function were analyzed. RESULTS: Compared to the other groups, RHR-S treated group showed significantly lower post-reperfusion aspartate aminotransferase levels in the reperfusion effluent and histologic findings of hepatocyte viability and lesser degree of congestion and necrosis. RHR-S resulted in a significantly higher mitochondrial respiratory control index and calcium retention capacity. Transcriptomic profile analysis showed that treatment with RHR-S activated cell survival and viability, cellular homeostasis as well as other biological functions involved in tissue repair such as cytoskeleton or cytoplasm organization, cell migration, transcription, and microtubule dynamics. Furthermore, RHR-S inhibited organismal death, morbidity and mortality, necrosis, and apoptosis. CONCLUSION: Subnormothermic RHR mitigates IRI and preserves hepatic mitochondrial function after warm and cold hepatic ischemia. This organ resuscitative therapy may also trigger the activation of protective genes against IRI. Sub- normothermic RHR has potential applicability to clinical liver transplantation.

Calcium Chloride Requirement and Postreperfusion Rebound During Massive Transfusion in Liver Transplantation.

OBJECTIVES: The administration of citrated blood products during massive transfusion requires calcium salt administration to prevent citrate toxicity and to maintain ionized calcium values. The literature does not provide adequate guidance for the amount of calcium required during massive transfusions during liver transplantation. This study was conducted to provide guidance on calcium salt replacement during a massive transfusion in liver transplant patients, with a focus on the phase of transplantation during which citrate metabolism was minimal. DESIGN: An observational retrospective chart review. SETTING: An academic single-institution study of hospitalized patients. PARTICIPANTS: One hundred thirty-two patients after liver transplantation. INTERVENTIONS: The study authors observed documented measurements of ionized calcium and observed the ratio of calcium salts to citrated bank blood products in patients undergoing liver transplantation with complete data sets. They also observed the effect of continuous venovenous hemofiltration on the distribution of ionized calcium values. MEASUREMENTS AND MAIN RESULTS: Prereperfusion, an average of 1.09 g CaCl2/L of citrated blood was administered to maintain ionized calcium in the normal range. Postreperfusion, less CaCl2 was administered, and a rebound of ionized calcium occurred. Prereperfusion, continuous venovenous hemofiltration reduced the number of ionized calcium values outside of 2 standard deviations, meaning fewer values were critically low. CONCLUSIONS: With massive transfusions up to 67 liters (approximately 13 blood volumes), 1.09 g CaCl2/L citrated blood maintained ionized calcium in the normal range in the absence of citrate metabolism. This ratio may have value in empiric treatment when ionized calcium measurements are unavailable, and massive transfusion rates exceed metabolic capacity.

Acetazolamide reduces postoperative pain following laparoscopic inguinal herniorrhaphy.

BACKGROUND: Carbonic acid accumulation, which results from CO2 insufflation, can produce visceral and referred pain in the postoperative setting. Acetazolamide inhibits carbonic anhydrase, an enzyme that accelerates carbonic acid formation. We hypothesized that preoperative administration of acetazolamide would decrease postoperative pain in patients undergoing laparoscopic inguinal herniorrhaphy. METHODS: A retrospective review was conducted of patients who underwent laparoscopic preperitoneal inguinal herniorrhaphy at the Medical College of Wisconsin between October 2012 and September 2014. Beginning in January 2014, patients began receiving 250 mg of acetazolamide preoperatively; patients prior to that time did not. The visual analog scale (range 0-10) was used to assess both preoperative pain and postoperative pain. RESULTS: A total of 66 patients underwent laparoscopic inguinal herniorrhaphy during the study interval. Of these, 22 (33 %) patients received acetazolamide preoperatively, and 44 (67 %) were included as controls. Overall mean pain scores were lower in the acetazolamide group (1.9 ± 1.45 vs 2.9 ± 1.5, p = 0.04). Specifically, patients who received acetazolamide reported lower pain scores immediately after surgery (0.6 ± 1.2 vs 1.9 ± 2.3, p = 0.01) and on post-op day one (2.3 ± 0.9 vs 4.0 ± 2.1, p = 0.04). Total morphine equivalents administered to manage postoperative pain were significantly less for the acetazolamide group (4.3 ± 4.8 mg) when compared to the control group (8.9 ± 8.4 mg), p = 0.04. Perioperative complications did not differ between the groups (p = 0.16). CONCLUSIONS: Acetazolamide appears to reduce pain in the immediate postoperative setting. Patients who received acetazolamide had lower pain scores postoperatively and required fewer narcotics for pain management prior to discharge.

Maintenance of Ionized Calcium During Prolonged Extreme Massive Transfusion During Liver Transplantation.

INTRODUCTION: Massive transfusion may cause ionized hypocalcemia, a complication that, when severe, causes hemodynamic instability. Extant literature fails to provide effective guidance on replacement strategies to avoid severe ionized hypocalcemia in the most extreme situations. CASE PRESENTATION: We discuss a liver transplant in which our empiric calcium replacement strategy resulted in no critically low ionized calcium values during the pre-reperfusion phase of a liver transplant with over 140 000 mL of bank blood transfusion, with an average of 10 000 mL per hour for 14 hours. DISCUSSION: Few comparable reports exist. Most rely upon monitoring with subsequent replacement, but these have not been effective at avoiding severely low ionized calcium values. CONCLUSIONS: Our empiric calcium replacement strategy of 1 gram of calcium chloride per liter of citrated bank blood transfused, in 200 mg/200 mL increments, resulted in successful maintenance of ionized calcium during the anhepatic phase of liver transplantation while on continuous veno-venous hemofiltration.

Anaphylaxis on reperfusion during liver transplantation with coagulopathy.

We present a case in which anaphylaxis on hepatic reperfusion during liver transplantation presented only with hypotension and coagulopathy. There were no cutaneous manifestations or clinical features distinguishing anaphylaxis from postreperfusion syndrome. The recipient regularly consumed seafood, and the organ donor died of anaphylaxis to shellfish. The trigger for anaphylaxis was postulated to be passive transfer of immunoglobulin to the recipient. Anesthesiologists should be notified of donor factors to anticipate anaphylaxis. In this report, we discuss coagulopathy of anaphylaxis and contrast it with disseminated intravascular coagulation.

Hydroxocobalamin for treatment of catecholamine-resistant vasoplegia during liver transplantation: A single-center series of 20 cases.

INTRODUCTION: Catecholamine-resistant vasoplegia is a potentially devastating complication during liver transplantation. Hydroxocobalamin has emerged as a treatment for vasoplegia associated with cardiac surgery, liver transplantation, and septic shock. PRESENTATION OF CASE: We performed a retrospective review of patients who underwent liver transplantation between October 2015 and May 2020 to evaluate the efficiency of hydroxocobalamin in this setting. DISCUSSION: A total of 137 patients underwent liver transplantation, of which 20 received hydroxocobalamin for vasoplegia. Administration of hydroxocobalamin increased mean arterial pressure and reduced vasoactive drug requirements. CONCLUSION: This case series adds to the previous individual reports describing the use of hydroxocobalamin during liver transplantation suggesting hydroxocobalamin can mitigate refractory hypotension from catecholamine resistant vasoplegia during liver transplantation.

A Case Report of Hypotension and Methemoglobinemia Associated With Gunshot Residue Poisoning: Nitrite-Induced Methemoglobinemia.

A patient with gunshots within inches of the skin developed intraoperative vasodilatory hypotension and methemoglobinemia, both recognized consequences of nitrite poisoning. A 1- mg/kg dose of methylene blue transiently and partially reversed methemoglobinemia, but the color of the methylene blue faded rapidly, consistent with bleaching of methylene blue by nitrite in vivo. Methylene blue did not raise blood pressure, consistent with inhibition of nitric oxide (NO) synthase. Because NO production from nitrite uses an NO synthase (NOS)-independent pathway, methylene blue is expected to have little effect on reversing hypotension from nitrite poisoning. Consider nitrite toxicity in gunshot patients with refractory vasodilatory hypotension and elevated methemoglobin.

Case report: Severe vasospasm mimics hypotension after high-dose intrauterine vasopressin.

Intramyometrial vasopressin injection reduces bleeding during myomectomy. Subsequent loss of peripheral pulses and nonmeasurable arterial blood pressure have been attributed to cardiovascular collapse or hypotension. When interpreted as global hypotension, treatment with vasopressors or according to Advanced Cardiac Life Support resuscitation protocols has been associated with cardiac complications. We describe a patient who developed loss of peripheral pulses and nonmeasurable blood pressure by noninvasive means after myometrial administration of 60 U vasopressin, with documented severe peripheral arterial vasospasm and elevated proximal blood pressure. We discuss the pathophysiology and emphasize the danger of misinterpreting pulselessness as global hypotension instead of vasospasm in this setting.

Difficult mask ventilation.

Mask ventilation is the most fundamental skill in airway management. In this review, we summarize the current knowledge about difficult mask ventilation (DMV) situations. Various definitions for DMV have been used in the literature. The lack of a precise standard definition creates a problem for studies on DMV and causes confusion in data communication and comparisons. DMV develops because of multiple factors that are technique related and/or airway related. Frequently, the pathogenesis involves a combination of these factors interacting to cause the final clinical picture. The reported incidence of DMV varies widely (from 0.08% to 15%) depending on the criteria used for its definition. Obesity, age older than 55 yr, history of snoring, lack of teeth, the presence of a beard, Mallampati Class III or IV, and abnormal mandibular protrusion test are all independent predictors of DMV. These signs should, therefore, be recognized and documented during the preoperative evaluation. DMV can be even more challenging in infants and children, because they develop hypoxemia much faster than adults. Finally, difficult tracheal intubation is more frequent in patients who experience DMV, and thus, clinicians should be familiar with the corrective measures and management options when faced with a challenging, difficult, or impossible mask ventilation situation.

Severe allergic contact dermatitis resulting from occupational exposure to tincture of benzoin aerosol spray in an anesthesiologist.

We describe the clinical presentation and management of an anesthesiologist who developed a severe allergic contact dermatitis resulting from occupational exposure to tincture of benzoin aerosol spray. A previously healthy male anesthesiologist with a small laceration between his right thumb and forefinger used a tincture of benzoin aerosol spray to improve adhesion of a small bandage immediately before performing a spinal anesthetic. He had previously used benzoin for skin reinforcement on several occasions during weight-lifting. The anesthesiologist experienced severe pruritus in the affected hand 48 h after benzoin exposure. A well-demarcated, bright red erythematous confluent vesicular dermatitis with and without painful hemorrhagic bullae erupted on the palmar and dorsal surfaces, respectively, of his hand, accompanied by pronounced edema. The palmar bullae were drained with several small incisions and the anesthesiologist was treated with intravenous methylprednisolone. He was unable to work for 10 days while the dermatitis gradually resolved. The case emphasizes that occupational exposure to benzoin represents a potential risk for operating room personnel who may be susceptible to cutaneous delayed hypersensitivity-mediated allergic reactions as a result of previous exposure to benzoin or chemically related cross-reacting substances.

Persistent Hypotension and Cerebral Swelling Resulting From Mesenteric Traction Syndrome After Omental-to-Pial Pedicle Flap Transfer in a Young Woman With Refractory Moyamoya Disease: A Case Report.

Superficial temporal arterial to middle cerebral arterial anastomosis is often the initial surgical treatment of Moyamoya disease. In refractory cases, placing a pedicle flap of omentum over the ischemic brain has resulted in clinical improvement or stabilization of symptoms. We present a case of persistent mesenteric traction syndrome manifested by hypotension unresponsive to conventional doses of vasopressors during and after pulling the omentum to the brain. As prostacyclin is a major mediator of hypotension from mesenteric traction syndrome and also a cerebral vasodilator, we discuss the possibility that brain swelling may be a manifestation of mesenteric traction syndrome.

Outcome analysis of continuous intraoperative renal replacement therapy in the highest acuity liver transplant recipients: A single-center experience.

BACKGROUND: Orthotopic liver transplantation is the definitive treatment modality for patients with end-stage liver disease. Pre-orthotopic liver transplantation renal dysfunction has a significant negative influence on outcomes post-orthotopic liver transplantation. Intraoperative renal replacement therapy is an adjunctive therapy to address the metabolic challenges during orthotopic liver transplantation in patients with a high acuity of illness. The impact of intraoperative renal replacement therapy on post-orthotopic liver transplantation outcomes, however, is unclear. METHODS: From October of 2012 to April of 2016, 96 adult patients underwent orthotopic liver transplantation for end-stage liver disease. Three groups were identified: (1) Group I: patients with pre-orthotopic liver transplantation renal dysfunction who underwent intraoperative renal replacement therapy, (2) Group II: patients with pre-orthotopic liver transplantation renal dysfunction who did not receive intraoperative renal replacement therapy, and (3) Group III: patients with orthotopic liver transplantation without evidence of pretransplant renal dysfunction. RESULTS: At 17.7 months follow-up, there was no difference in survival among the study groups. Physiologic model for end-stage liver disease at the time of orthotopic liver transplantation was significantly higher in both groups with renal dysfunction (I = 43, II = 39) than in Group III (18). Post-orthotopic liver transplantation, 12-month patient survival in Group II was 100%. While the model for end-stage liver disease score at orthotopic liver transplantation was significantly different between Group I and Group III, the 12-month, post-orthotopic liver transplantation patient survival was comparable at 78% vs 88%, respectively. CONCLUSION: Intraoperative renal replacement therapy is a safe adjunctive therapy during liver transplantation of critically ill patients with renal dysfunction. Identifying patients who require intraoperative renal replacement therapy would improve intraoperative and post-liver transplant survival and may facilitate recovery of native kidney function after transplant.

Hydroxocobalamin for Vasoplegic Syndrome in Liver Transplantation: Restoration of Blood Pressure Without Vasospasm.

Systemic vasoplegia is common in patients undergoing liver transplantation. In this report, we present a case in which treatment with conventional vasopressors caused peripheral arterial spasm, rendering arterial blood pressure monitoring impossible. Administration of methylene blue resolved the vasospasm; however, concern for toxic dose requirements limited its use. Hydroxocobalamin administration resolved the vasospasm and increased blood pressure without the potential adverse effects seen with methylene blue. This case represents the first report of hydroxocobalamin use in liver transplantation and may represent a new option for the treatment of vasoplegia and the potential vasospasm that may result from traditional vasopressors.