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M Rosenblum

Publications and source records attributed to M Rosenblum.

At least 19 recordsLinked to original sources
PubMed2000

Spinal cord injury in rat: treatment with bone marrow stromal cell transplantation.

We tested the hypothesis that transplantation of bone marrow stromal cells (MSCs) into the spinal cord after a contusion injury promotes functional outcome. Rats (n = 31) were subjected to a weight driven implant injury. MSCs or phosphate buffered saline was injected into the spinal cord 1 week after injury. Sections of tissue were analyzed by double-labeled immunohistochemistry for MSC identification. Functional outcome measurements using the Basso-Beattie-Bresnehan score were performed weekly to 5 weeks post-injury. The data indicate significant improvement in functional outcome in animals treated with MSC transplantation compared to control animals. Scattered cells derived from MSCs expressed neural protein markers. These data suggest that transplantation of MSCs may have a therapeutic role after spinal cord injury.

Animals↗
PubMed2000

Rolandic encephalopathy and epilepsia partialis continua following bone marrow transplant.

Epilepsia partialis continua (EPC) is a condition defined by prolonged focal myoclonus. Often resistant to therapy, EPC in children is frequently present in Rasmussen encephalitis, a form of chronic encephalitis of uncertain etiology. We discuss a child who developed bilateral EPC 5 months after a bone marrow transplant. Neuroimaging studies showed signal abnormalities on both sensory-motor areas. An extensive search failed to reveal the etiology of the disorder, but treatment with a broad-spectrum anti-viral agent was associated with resolution of the process. An unidentified infectious agent may be responsible for an encephalitis of the motor strip in immunosuppressed patients.

Bone Marrow Transplantation↗
PubMed1999

Regimen-related toxicity of myeloablative chemotherapy with BCNU, thiotepa, and etoposide followed by autologous stem cell rescue for children with newly diagnosed glioblastoma multiforme: report from the Children's Cancer Group.

BACKGROUND: The survival of children with glioblastoma multiforme (GBM) remains poor. In an effort to improve the cure rate of children with this disease, high-dose chemotherapy followed by autologous stem cell rescue (ASCR) has been evaluated. We report the regimen-related toxicity (RRT) and survival seen in 11 children with newly diagnosed GBM treated with high-dose chemotherapy on a Children's Cancer Group study (CCG-9922). PROCEDURES: This phase II pilot study, intended to treat 30 patients, accrued 11 patients from July, 1993, to April, 1995. The pre-ASCR preparative regimen included BCNU 100 mg/m2 every 12 hr for a total of six doses on days -8, -7, -6; thiotepa 300 mg/m2/day on days -5, -4, -3; and etoposide 250 mg/m2/day on days -5, -4, -3. All patients received delayed radiotherapy at a dose of 5,400 cGy to the primary site commencing on approximately day +42 after ASCR. RESULTS: Five patients (45%) developed significant, nonfatal (grade III or IV) pulmonary and/or neurological toxicities. Three patients developed signs and/or symptoms of idiopathic interstitial pneumonitis. Eight patients (73%) have died, two (18%) of toxicity, and six (55%) of disease progression. Three patients (27%) achieved and remain in complete radiographic remission 2.9, 3.9, and 5.1 years from ASCR. One of these three, developed a lymphoblastic non-Hodgkins lymphoma (NHL) 3. 5 years post-ASCR. The survival rates for these 11 children at 1 year and 2 years are 73% +/- 13% and 46% +/- 14%, respectively. The progression-free survival rates at 1 year and at 2 years are 64% +/- 14% and 46% +/- 14%, respectively. CONCLUSIONS: We conclude that high-dose chemotherapeutic regimens followed by ASCR is a feasible treatment of childhood GBM. The BCNU-based preparative regimen utilized in this study was associated with prohibitive pulmonary toxicity.

Adolescent↗
PubMed1999

Safety, pharmacokinetics, and tissue distribution of liposomal P-ethoxy antisense oligonucleotides targeted to Bcl-2.

Antisense oligonucleotides (oligos) have the ability to selectively block disease-causing genes, thereby inhibiting production of disease-associated proteins. However, their effectiveness has been limited by their low intracellular delivery. We had previously demonstrated that liposomes could increase the intracellular uptake of P-ethoxy oligos, hydrophobic analogs of phosphodiesters, and that liposomal Bcl-2 P-ethoxy antisense oligos (L-Bcl-2) could selectively inhibit Bcl-2 protein production, thereby inducing growth inhibition in Follicular Lymphoma cell lines. To understand the in vivo behavior of L-Bcl-2, we conducted a series of studies to evaluate the safety, pharmacokinetics, and tissue distribution of i.v. injections of L-Bcl-2 in normal rodents. Daily administration of 20 mg of L-Bcl-2/kg of body weight in 5 consecutive days had no adverse effects on renal or hepatic functions, nor on hematological parameters. Histopathology also did not reveal any significant changes in the morphology of the organs studied. In rats, the area under the curve of L-Bcl-2 reflects a two-compartment model of distribution with a biphasic plasma clearance. The T(1/2alpha) and T(1/2beta) were approximately 8 min and 4.2 h, respectively, and the V(d) was 79 ml, indicating a broad body distribution. The highest concentrations of L-Bcl-2 were found in spleen > liver > kidneys. These studies showed that in the schedules studied no significant toxicity associated with L-Bcl-2 was observed over 6 weeks, and that L-Bcl-2 could be widely distributed in the body.

Animals↗
PubMed1998

Subcutaneous administration of midazolam: a comparison of the Bioject jet injector with the conventional syringe and needle.

PURPOSE: The purpose of this study was to compare jet injection to a syringe and needle in terms of the difference in discomfort and pharmacokinetics after the subcutaneous administration of midazolam. PATIENTS AND METHODS: Using a prospective, randomized, double-blinded study design, 14 subjects were administered midazolam on two separate occasions (at least 2 weeks apart). The subjects were randomly distributed into two groups: syringe and needle (saline)/jet injector (midazolam) or syringe and needle (midazolam)/jet injector (saline). The subjects were randomly assigned to receive either EMLA (eutectic mixture of local anesthetics) or a placebo at the injection site for the first administration and the other topical agent on the second visit. Each subject received one subcutaneous injection in the deltoid region per arm per day. Each injection contained the same volume of solution. Subjects completed visual analog scale (VAS) questionnaires assessing the discomfort of the injection. Blood samples were taken at specified intervals over 2 hours for determination of midazolam levels. RESULTS: The discomfort associated with the injection was less with the Biojector 2000 (Bioject Inc, Portland, OR) although this was not statistically significant. However, persistent discomfort was significantly greater at the needle site. The mean peak plasma level of midazolam was achieved more rapidly with the Biojector 2000 than with the syringe and needle (P < .05). However, the peak plasma level after jet injection or injection with a syringe and needle was not statistically different. CONCLUSION: The results of the study show that the Biojector 2000 is a needle-free injection system that can be used for the administration of a premedicant before induction of anesthesia. It has several advantages, including the potential reduction of anxiety associated with the "fear of needles" and occupational injuries.

Adolescent↗
PubMed1998

Intensive chemotherapy and bone marrow rescue for young children with newly diagnosed malignant brain tumors.

PURPOSE: To evaluate a strategy that avoids radiotherapy in children less than 6 years of age with newly diagnosed malignant brain tumors, by administering myeloablative consolidation chemotherapy with autologous bone marrow reconstitution (ABMR) after maximal surgical resection and conventional induction chemotherapy. PATIENTS AND METHODS: Between March 1991 and April 1995, 62 children (median age, 30 months) with newly diagnosed malignant brain tumors were enrolled onto this trial. Children received conventional induction chemotherapy with vincristine, cisplatin, cyclophosphamide, and etoposide, repeated every 3 weeks for five cycles. Children without disease progression on induction chemotherapy were offered consolidation with myeloablative chemotherapy that incorporated carboplatin, thiotepa, and etoposide followed by ABMR. Irradiation was used only for residual tumor at consolidation or for progressive/recurrent disease. RESULTS: Induction chemotherapy was well tolerated by most patients; however, progression was noted in 17 children (27%) and four (6%) died of treatment complications. Of 37 children who received consolidation chemotherapy with ABMR, 15 are free of disease progression (median post-ABMR without further treatment, >44 months). The remaining 22 all progressed within 15 months of ABMR; three of 37 (8%) died of treatment-related complications. The 3-year overall survival (OS) and event-free survival (EFS) rates from diagnosis for all children are 40% (95% confidence interval [CI], 28% to 52%) and 25% (95% CI, 13% to 37%), respectively. Radiotherapy was administered to 19 of 62 children: 17 for progressive disease (PD) and two for residual disease at the time of ABMR. CONCLUSION: A significant proportion of children with malignant brain tumors can avoid radiotherapy and prolonged maintenance chemotherapy yet still achieve durable remission with this brief intensive chemotherapy regimen.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

High-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue for patients with recurrent medulloblastoma. Children's Cancer Group.

PURPOSE: Medulloblastoma is a highly lethal disease when it recurs. Very few patients survive with conventional treatment. This study evaluated the use of high-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue (ASCR) in patients with recurrent medulloblastoma. METHODS: Chemotherapy consisted of carboplatin 500 mg/m2 (or area under the curve = 7 mg/mL x min via Calvert formula) on days -8, -7, and -6; and thiotepa 300 mg/m2 and etoposide 250 mg/m2 on days -5, -4, and -3; followed by ASCR on day 0. In addition to the study-prescribed therapy, 21 patients received other treatment: neurosurgical resection in seven, conventional chemotherapy in 17, and external-beam irradiation in 11 cases. RESULTS: Twenty-three patients with recurrent medulloblastoma, aged two to 44 years (median, 13 years) at ASCR, were treated. Three patients died of treatment-related toxicities within 21 days of ASCR; multiorgan system failure in two, and Aspergillus infection with venoocclusive disease in one. Seven of 23 patients (30%) are event-free survivors at a median of 54 months post-ASCR (range, 24 to 78 months). Kaplan-Meier estimates of event-free (EFS) and overall survival are 34% +/- 10% and 46% +/- 11%, respectively, at 36 months post-ASCR. CONCLUSION: This strategy may provide long-term survival for some patients with recurrent medulloblastoma.

Adolescent↗
PubMed1998

Myeloablative chemotherapy with autologous bone marrow rescue in young children with recurrent malignant brain tumors.

PURPOSE: This study evaluates the outcome of myeloablative chemotherapy and autologous bone marrow rescue (ABMR) with or without radiotherapy in children younger than 6 years of age with recurrent malignant brain tumors who had not previously been exposed to conventional fractionated external-beam irradiation. PATIENTS AND METHODS: Patients underwent surgery and/or conventional chemotherapy at the time of recurrence to achieve minimal residual disease (two of these patients also underwent local single-fraction gamma-knife radiosurgery). Myeloablative chemotherapy was then administered with carboplatin, thiotepa, and etoposide (16 patients), thiotepa and etoposide (three patients), or thiotepa, etoposide, and carmustine (BCNU; one patient). Autologous bone marrow was re-infused 72 hours after chemotherapy. Twelve patients received external-beam irradiation after recovery from ABMR. RESULTS: Twenty patients with recurrent brain tumors aged 0.7 to 5.9 years (median, 2.9 years) at ABMR were evaluated. Two patients died of toxicity related to myeloablative therapy. Eight patients died of progressive disease. Ten of 20 (50%) patients (primitive neuroectodermal tumor (PNET)/medulloblastoma, three patients; cerebral PNET, three patients; glioblastoma multiforme, two patients; anaplastic astrocytoma, one patient; pineal PNET, one patient) are alive and disease free at a median of 37.9 months (range, 9.7 to 98.2 months) from ABMR (3-year overall survival [OS] rate of 43% +/- 13% and event-free survival [EFS] rate of 47% +/- 14%]. Seven of these 10 patients also received irradiation post-ABMR. CONCLUSION: Myeloablative chemotherapy with ABMR followed by additional external-beam irradiation appears to be an effective retrieval therapy for some young children with recurrent malignant brain tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Intraperitoneal immunotherapy of peritoneal carcinomatosis.

Carcinomas that originate in the ovary or from different sites in the gastrointestinal tract frequently develop metastases that involve the peritoneal and serosal surfaces. Carcinomatous involvement of the peritoneum is a significant cause of morbidity and mortality. Advances in our understanding of the immunobiology of the peritoneal cavity and the availability of technically advanced immunotherapeutic agents are providing an important opportunity for the intraperitoneal delivery of these agents. This review describes newer concepts in tumor immunology that have a bearing on the further development of intraperitoneal immunotherapy; delivery systems for and issues to be resolved in intraperitoneal immunotherapy, and results of studies with recombinant interferons alpha and gamma and interleukin (IL)-2, cellular therapies including lymphokine-activated killer cells, tumor-infiltrating lymphocytes, monoclonal antibodies, and intraperitoneal radioimmunotherapy. New trials of intraperitoneal immunotherapy employing novel agents, including IL-12 and genetically modified tumor vaccines, are discussed, as are issues related to the integration of immunotherapy with standard chemotherapy agents. A number of immunotherapy agents have been tested intraperitoneally and have shown promising clinical activity with acceptable toxicity. Complete responses have been documented at surgical restaging, and intraperitoneal treatments with these agents may soon be included in the therapeutic armamentarium for patients with peritoneal carcinomatosis.

Carcinoma↗
PubMed1997

Intensely cytotoxic anthracycline prodrugs: glucuronides.

We previously reported the synthesis of a series of doxorubicin analogue prodrugs that give rise to intensely cytotoxic metabolites in the presence of carboxylate esterases. We now report studies on structurally related beta-glucuronide prodrugs that are converted to similar potent metabolites in the presence of beta-glucuronidases. These prodrugs were prepared by reductive condensation of daunomycin or doxorubicin with methyl 1-O-[(1'RS)-1'-ethoxy-4'-oxobutyl]-2,3,4-tri-O-acetyl-beta-D- glucopyranosyluronate in the presence of sodium cyanoborohydride followed by base-mediated cleavage of the glucuronate protective groups. The doxorubicin derivatives were isolated in very low yield, most likely because of the inherent base lability of the parent aglycone. By contrast, fairly good yields of the more base-stable daunomycin analogues were obtained. The target daunomycin glucuronide, N-[(4"RS)-4"-ethoxy-4"-(sodium 1"'-O-beta-D-glucopyranuronate)butyl]daunorubicin (6a), had a half-life of 30 h when incubated at a concentration of 12 microM in aqueous 0.05 M phosphate buffer, pH 7.4, at 37 degrees C. Under identical conditions in the presence of 197 units/mumol of Escherichia coli beta-glucuronidase, 6a was hydrolyzed with a half-life of 1.7 h. The single metabolite observed was chromatographically identical with that formed from the hydrolysis of N-(4,4-diacetoxybut-1-yl)daunomycin by carboxylate esterases. 6a was approximately 10,000-fold more toxic to human A375 melanoma cells in the presence of E. coli beta-glucuronidase than in the absence of the enzyme. These findings indicate the therapeutic potential of anthracycline glucuronide prodrugs as independent entities or four use in conjunction with enzyme tissue-targeting strategies such as antibody-directed enzyme prodrug therapy (ADEPT) or gene-directed enzyme prodrug therapy (GDEPT).

Antibiotics, Antineoplastic↗
PubMed1997

Pharmacokinetics and acute toxicology of intraventricular 131 I-monoclonal antibody targeting disialoganglioside in non-human primates.

Tumors metastatic to the leptomeninges are often incurable despite current aggressive treatment modalities. Regional therapy by intrathecal administration of monoclonal antibodies (MoAbs) can maximize their concentration to tumor sites while reducing systemic toxicities. Anti-GD2 antibody 3F8 has successfully targeted human neuroectoderm derived tumors. Disialoganglioside GD2 expression in the central nervous system is identical between humans and cynomolgus monkeys. We studied the pharmacokinetics and the acute and subacute toxicities of intraventricular 131I-3F8 in 8 cynomolgus monkeys. Four animals were purposely immunized with intravenous 3F8 administered 2-4 weeks prior to injections. All animals remained clinically stable. Toxicities included weight loss, fever and CSF leukocytosis. One animal developed a left-sided hemiparesis following his seventh injection, presumably due to a local drug accumulation in the setting of an intermittently patent catheter. The estimated radiation dose to the CSF was 19-48 Gy in the immunized monkeys and 19-82 Gy in the nonimmunized monkeys, and to blood was 0.11-0.98 Gy and 0.29-2.03 Gy, respectively. Histopathology revealed chronic reactive changes adjacent to the region of catheter placement and a focal vasculitis in 2 animals. Peripheral blood counts and bone marrow examinations remained normal. Because of the blood-brain barrier, CSF monkey-anti-mouse antibody titers were less than 10 per cent of those in the serum. In contrast to the CSF radioactivity clearance which was similar in all animals, blood clearance was substantially accelerated in 3F8-immunized animals versus controls. Correspondingly, the CSF to blood dose ratio was improved 1.3 to 6.6 fold (mean 3.5). We conclude that intraventricular administration of 131I-3F8 in primates is tolerable. It can deliver very high doses of radiation to the CSF space with minimal toxicity to blood and bone marrow. Serum anti-mouse antibody accelerates the clearance of 131I-3F8 in blood and may improve the therapeutic index.

Animals↗
PubMed1996

Alterations in tretinoin pharmacokinetics following administration of liposomal all-trans retinoic acid.

We administered liposome-encapsulated all-trans retinoic acid (L-ATRA) to 48 patients with refractory hematologic malignancies using an every-other-day schedule for 28 days and doses of 15 to 175 mg/m2. In 19 patients, pharmacology studies were conducted after the first (day 1) and seventh (day 15) doses. In contrast to the decline in tretinoin concentration seen within 3 to 4 days of administration of daily oral ATRA, there were no differences between the area under the curve (AUC) of tretinoin concentration versus time on day 1 and day 15 (P = .98, Wilcoxon signed-rank test). Peak day 1 concentrations after 15 mg/m2 were higher than those reported after 45 mg/m2 oral ATRA. Six patients with relapsed acute promyelocytic leukemia (APL) were treated. Three, each in first relapse and at least year from the last exposure to oral ATRA, achieved a complete response (CR). Disease recurred in two (one at 3 months despite maintenance L-ATRA and similarity in tretinoin AUC on days 1 and 85, and the other at 5 months, 2 months after discontinuation of L-ATRA) and the third was transplanted 1 month into CR. The three nonresponders were in at least a second relapse and failed to respond to oral ATRA before or immediately after receiving L-ATRA. Severe toxicity developed in three of eight patients treated at 175 mg/m2 (joint pains in two, skin in one). The maximum tolerated dose (MTD) was determined to be 140 mg/m2, at which dose grade 2 toxicity (primarily headache and skin) occurred in eight of eight patients, but grade 3 to 4 toxicity in none. Compared with oral ATRA, L-ATRA apparently results in greater exposure to tretinoin and for a longer time.

Drug Carriers↗
PubMed1996

Chemotherapy without irradiation--a novel approach for newly diagnosed CNS germ cell tumors: results of an international cooperative trial. The First International Central Nervous System Germ Cell Tumor Study.

PURPOSE: Radiation therapy for CNS germ cell tumors (GCT) is commonly associated with neurologic sequelae. We designed a therapeutic trial to determine whether irradiation could be avoided. PATIENTS AND METHODS: Patients received four cycles of carboplatin, etoposide, and bleomycin. Those with a complete response (CR) received two further cycles; others received two cycles intensified by cyclophosphamide. RESULTS: Seventy-one patients were enrolled (45 with germinoma and 26 with nongerminomatous GCT [NGGCT]). Sixty-eight were assessable for response. Thirty-nine of 68 (57%) achieved a CR within four cycles. Of 29 patients with less than a CR, 16 achieved CR with intensified chemotherapy or second surgery. Overall, 55 of 71 (78%) achieved a CR without irradiation. The CR rate was 84% for germinomas and 78% for NGGCT. With a median follow-up duration of 31 months, 28 of 71 patients were alive without relapse or progression. Thirty-five showed tumor recurrence (n = 28) or progression (n = 7) at a median of 13 months. Twenty-six of 28 patients (93%) who recurred following remission underwent successful salvage therapy. Pathology was the only variable predictive of survival. The probability of surviving 2 years was .84 for germinoma patients and .62 for NGGCT. Seven of 71 patients died of toxicity associated with study chemotherapy. CONCLUSION: Forty-one percent of surviving patients and 50% of all patients were treated successfully with chemotherapy only without irradiation. Chemotherapy-only regimens for CNS GCT, although encouraging, should continue to be used only in the setting of formal clinical trials.

Adolescent↗
PubMed1995

AIDS dementia complex and HIV-1 brain infection: clinical-virological correlations.

To evaluate the presence and distribution of central nervous system infection by human immunodeficiency virus type 1 (HIV-1), we used immunohistochemical methods to map the HIV-1 p24 core protein in the brains of 55 autopsied patients with acquired immunodeficiency syndrome (AIDS). In a subset of 40 of these patients who had undergone antemortem neurological evaluation of the AIDS dementia complex (ADC), we analyzed the relation between the severities of the viral infection and clinical dysfunction. Viral antigen was detected in macrophages and cells with morphological and immunohistochemical characteristics of microglia as well as multinucleated cells. The distribution of antigen-positive cells preferentially involved certain deep brain structures, especially the globus pallidus, other basal ganglia nuclei, and the central white matter. Overall, the presence and frequency of infected cells were highly correlated with the histological findings of multinucleated-cell encephalitis and in general with the clinical ADC stage. However, infection was often more limited than might be "anticipated" from the severity of patients' clinical dysfunction: Only 61% of patients with at least ADC stage 1 had detectable antigen and of these only approximately 30% of the brain sections were antigen positive. These results suggest a pathogenetic model of ADC where virus- or cell-coded toxins amplify the effect of limited brain infection.

AIDS Dementia Complex↗
PubMed1995

The impact of heparin concentration and activated clotting time monitoring on blood conservation. A prospective, randomized evaluation in patients undergoing cardiac operation.

A whole blood hemostasis system (Hepcon) provides both activated clotting time and accurate whole blood heparin concentration measurements via an automated protamine titration method. This study was designed to prospectively evaluate the impact of heparin and protamine administration using this system on the incidence and treatment of bleeding after cardiopulmonary bypass. Two hundred fifty-four patients requiring cardiopulmonary bypass were enrolled in this prospective study over a 7-month period. Patients treated with antifibrinolytic agents (aprotinin, epsilon-aminocaproic or tranexamic acid) were excluded. Patients were randomly assigned to either a control (n = 127) or intervention (n = 127) group. For control patients, the anticoagulation protocol consisted of an initial fixed dose of 250 U/kg of heparin, and additional 5000 U heparin doses were administered if the activated clotting time was less than 480 seconds. Heparin was neutralized with an initial fixed dose of protamine (0.8 mg protamine per milligram total heparin). For the intervention group, an initial dose of heparin was based on an automated heparin dose-response assay. Additional heparin doses were administered if the heparin concentration was less than the reference concentration or for an activated clotting time less than 480 seconds. The protamine dose was based on the residual heparin concentration. Treatment of excessive bleeding after cardiopulmonary bypass was based on an algorithm using point-of-care testing with whole blood prothrombin time, activated partial thromboplastin time, heparinase activated clotting time, and platelet count. No differences between the two treatment groups were identified in reference to demographic factors, preoperative anticoagulant medications, preoperative coagulation data, number of reoperations, or combined procedures and duration of cardiopulmonary bypass. Indirect evidence for coagulation factor consumption was demonstrated in control patients by more prolonged whole blood prothrombin time and activated partial thromboplastin time values after cardiopulmonary bypass when compared with values obtained in the intervention group. Patients in the intervention cohort received greater doses of heparin (intervention: 612 +/- 147, control: 462 +/- 114 U/kg, p < 0.0001) and had lower protamine to heparin ratios (intervention: 0.70 +/- 0.64, control: 0.94 +/- 0.21, p = 0.0001) compared with control patients. Patients in the intervention cohort received significantly fewer platelet (intervention: 1.7 +/- 3.6 U, control: 3.7 +/- 6.7 U, p = 0.003), plasma (intervention: 0.4 +/- 1.3 U, control: 1.4 +/- 2.5 U, p = 0.0001), and cryoprecipitate units (intervention: 0.0 +/- 0.0 U, control: 0.2 +/- 1.2 U, p = 0.04) during the perioperative interval than control patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1995

Activation of the Bezold-Jarisch reflex in the sitting position for shoulder arthroscopy using interscalene block.

A retrospective analysis of 116 patients who underwent shoulder arthroscopy in the sitting position with interscalene block (ISB) revealed 20 patients who experienced potentially dangerous vasovagal events characterized by sudden severe hypotension and bradycardia (Group 1). The event occurred 61 +/- 18 min after the block placement. Ninety-six patients (Group 2) did not experience a vasovagal event. Of the patients in Group 2, 18 received beta-adrenergic blockers for increasing heart rate and/or arterial blood pressure (Group 2B) while 78 did not (Group 2A). The number receiving beta-adrenergic blockers was significantly greater than in Group 1 (18/96 vs 0/20, P < 0.05). There were no significant demographic or baseline hemodynamic differences between groups, but the beta-adrenergic blocker and vagal groups showed significantly greater intraoperative peak heart rates (P < 0.05). All patients received epinephrine in their local anesthetic for ISB, incision sites, and articular irrigating solution. Total and weight-corrected epinephrine doses differed significantly between groups (lowest in Group 2A, P < 0.01). Activation of the Bezold-Jarisch reflex, induced by increased circulating epinephrine levels and the sitting position, is the postulated mechanism.

Adult↗