RESUMO
STUDY DESIGN: Prospective, single-center study. OBJECTIVE: To evaluate the clinical relevance of the validated intraoperative bleeding severity scale (VIBe) in thoracolumbar spine surgery. METHODS: Adult patients aged 18 through 88 undergoing elective decompression, instrumentation, and fusion of the thoracolumbar spine were prospectively enrolled after informed consent was provided and written consent was obtained. Validated intraoperative bleeding severity scores were recorded intraoperatively. Univariate analysis consisted of Student T-tests, Pearson's χ2 Tests, Fisher's Exact Tests, linear regression, and binary logistic regression. Multivariable regression was conducted to adjust for baseline characteristics and potential confounding variables. RESULTS: A total of N = 121 patients were enrolled and included in the analysis. After adjusting for confounders, VIBe scores were correlated with an increased likelihood of intraoperative blood transfusion (ß = 2.46, P = .012), postoperative blood transfusion (ß = 2.36, P = .015), any transfusion (ß = 2.49, P < .001), total transfusion volume (ß = 180.8, P = .020), and estimated blood loss (EBL) (ß = 409, P < .001). Validated intraoperative bleeding severity scores had no significant association with length of hospital stay, 30-day readmission, 30-day reoperation, 30-day emergency department visit, change in pre- to post-op hemoglobin and hematocrit, total drain output, or length of surgery. CONCLUSION: The VIBe scale is associated with perioperative transfusion rates and EBL in patients undergoing thoracolumbar spine surgery. Overall, the VIBe scale has clinically relevant meaning in spine surgery, and shows potential utility in clinical research. LEVEL OF EVIDENCE: Level II.
RESUMO
BACKGROUND AND OBJECTIVES: Free-hand placement of T1 pedicle screws can often be challenging. A reliable free-hand technique for placement of T1 pedicle screws can overcome some of the difficulties associated with poor fluoroscopy in this region. The purpose of this study was to propose a novel anatomic landmark for accurate identification of the T1 entry point using the midpoint of the C7 lateral mass as a reference point. Our hypothesis is that the midpoint of the C7 lateral mass is within 1-2 mm of the center of the T1 pedicle. METHODS: Using 3-dimensional reconstruction software, the pedicle of T1 and the lateral mass of C7 were isolated to assess the location of the T1 pedicle relative to the C7 lateral mass. Specifically, the distance between the center of the T1 pedicle and the center of the C7 lateral mass was measured on 40 computed tomography scans. Furthermore, a clinical validation of this technique was performed by assessing the postoperative computed tomography scans of 53 patients undergoing cervicothoracic instrumentation. The Gertzbein and Robbins classification system was used to grade the accuracy of T1 pedicle screw placements in all patients using this technique. RESULTS: The average horizontal deviation + SD from centers of the T1 pedicle and the C7 lateral mass was 0.398 mm ± 0.953 mm. The T1 pedicle on average was slightly medial to the center of the C7 lateral mass. A total of 98.1% of T1 pedicle screws placed in vivo using the free-hand technique were of Grade A. CONCLUSION: In this article, we demonstrate that the center of the C7 lateral mass overlays the T1 pedicle and the optimal entry point is immediately below the midpoint of the C7 lateral mass. This approach provides a practical and accurate landmark in posterior cervicothoracic spine procedures that reduce the need for additional radiation exposure or increased operative time with image-guided techniques.
Assuntos
Parafusos Pediculares , Fusão Vertebral , Humanos , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Tomografia Computadorizada por Raios X , Fluoroscopia , Fusão Vertebral/métodosRESUMO
BACKGROUND: Spinal surgeries are being offered to a broader patient population who are both medically and surgically complex. History of prior spinal surgery, advanced age, and presence of comorbidities, such as obesity, malnutrition, steroid use, and tobacco use, are risk factors for postoperative complications. Prophylactic spinal reconstruction at the time of spinal surgery has been shown to have improved outcomes and decreased wound complications; however, outcomes focusing specifically on complex patients with a history of previous spinal surgery (or surgeries) have not been well described. METHODS: This is a retrospective study performed at the University of Maryland Medical Center (Baltimore, MD) of high-risk patients who underwent complex spinal surgery with prophylactic spinal reconstruction from 2011 to 2022. One hundred forty-three consecutive surgeries from 136 patients were included in the study. Patients younger than 17 years or who had an incomplete medical record were excluded. RESULTS: Most patients were female (63.6%) versus male (31.5%). The average American Society of Anesthesiologists score was 3. All but 6 patients (11%) had a history of at least 1 spinal surgery, with nearly half of patients having had between 2 and 5 spinal surgeries. Reconstruction was performed with paraspinous flaps in most cases (n = 133 [93%]). The overall complication rate was 10.5%, with surgical site infection being the most common complication. Seventeen patients (12.5%) underwent reoperation within 90 days of initial surgery. Average length of follow-up was 4.18 months (range, 0.03-40.53 months). CONCLUSIONS: In appropriately selected patients, prophylactic spinal reconstruction offers improved outcomes with decreased wound complications compared with salvage. For large defects, paraspinous flaps are recommended over other reconstructive options. Prolonged drain placement is felt to be protective against complications.
RESUMO
Expansion duraplasty to reopen effaced subarachnoid space and improve spinal cord perfusion, autoregulation, and spinal pressure reactivity index (sPRX) has been advocated in patients with traumatic cervical spinal cord injury (tCSCI). We designed this study to identify candidates for expansion duraplasty, based on the absence of cerebrospinal fluid (CSF) interface around the spinal cord on magnetic resonance imaging (MRI), in the setting of otherwise adequate bony decompression. Over a 61-month period, 104 consecutive American Spinal Injury Association Impairment Scale (AIS) grades A-C patients with tCSCI had post-operative MRI to assess the adequacy of surgical decompression. Their mean age was 53.4 years, and 89% were male. Sixty-one patients had falls, 31 motor vehicle collisions, 11 sport injuries, and one an assault. The AIS grade was A in 56, B in 18, and C in 30 patients. Fifty-four patients had fracture dislocations; there was no evidence of skeletal injury in 50 patients. Mean intramedullary lesion length (IMLL) was 46.9 (standard deviation = 19.4) mm. Median time from injury to decompression was 17 h (interquartile range 15.2 h). After surgery, 94 patients had adequate decompression as judged by the presence of CSF anterior and posterior to the spinal cord, whereas 10 patients had effacement of the subarachnoid space at the injury epicenter. In two patients whose decompression was not definitive and post-operative MRI indicated inadequate decompression, expansion duraplasty was performed. Candidates for expansion duraplasty (i.e., those with inadequate decompression) were significantly younger (p < 0.0001), were AIS grade A (p < 0.0016), had either sport injuries (six patients) or motor vehicle collisions (three patients) (p < 0.0001), had fracture dislocation (p = 0.00016), and had longer IMLL (p = 0.0097). In regression models, patients with sport injuries and inadequate decompression were suitable candidates for expansion duraplasty (p = 0.03). Further, 9.6% of patients failed bony decompression alone and either did (2) or would have (8) benefited from expansion duraplasty.
Assuntos
Medula Cervical , Lesões do Pescoço , Traumatismos da Medula Espinal , Traumatismos da Coluna Vertebral , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Medula Cervical/lesões , Traumatismos da Medula Espinal/cirurgia , Traumatismos da Medula Espinal/patologia , Descompressão Cirúrgica/métodos , Traumatismos da Coluna Vertebral/cirurgia , Resultado do Tratamento , Estudos RetrospectivosRESUMO
The therapeutic significance of timing of decompression in acute traumatic central cord syndrome (ATCCS) caused by spinal stenosis remains unsettled. We retrospectively examined a homogenous cohort of patients with ATCCS and magnetic resonance imaging (MRI) evidence of post-treatment spinal cord decompression to determine whether timing of decompression played a significant role in American Spinal Injury Association (ASIA) motor score (AMS) 6 months following trauma. We used the t test, analysis of variance, Pearson correlation coefficient, and multiple regression for statistical analysis. During a 19-year period, 101 patients with ATCCS, admission ASIA Impairment Scale (AIS) grades C and D, and an admission AMS of ≤95 were surgically decompressed. Twenty-four of 101 patients had an AIS grade C injury. Eighty-two patients were males, the mean age of patients was 57.9 years, and 69 patients had had a fall. AMS at admission was 68.3 (standard deviation [SD] 23.4); upper extremities (UE) 28.6 (SD 14.7), and lower extremities (LE) 41.0 (SD 12.7). AMS at the latest follow-up was 93.1 (SD 12.8), UE 45.4 (SD 7.6), and LE 47.9 (SD 6.6). Mean number of stenotic segments was 2.8, mean canal compromise was 38.6% (SD 8.7%), and mean intramedullary lesion length (IMLL) was 23 mm (SD 11). Thirty-six of 101 patients had decompression within 24 h, 38 patients had decompression between 25 and 72 h, and 27 patients had decompression >72 h after injury. Demographics, etiology, AMS, AIS grade, morphometry, lesion length, surgical technique, steroid protocol, and follow-up AMS were not statistically different between groups treated at different times. We analyzed the effect size of timing of decompression categorically and in a continuous fashion. There was no significant effect of the timing of decompression on follow-up AMS. Only AMS at admission determined AMS at follow-up (coefficient = 0.31; 95% confidence interval [CI]:0.21; p = 0.001). We conclude that timing of decompression in ATCCS caused by spinal stenosis has little bearing on ultimate AMS at follow-up.
Assuntos
Síndrome Medular Central/diagnóstico por imagem , Síndrome Medular Central/cirurgia , Descompressão Cirúrgica , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/cirurgia , Tempo para o Tratamento , Idoso , Síndrome Medular Central/etiologia , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Atividade Motora , Recuperação de Função Fisiológica , Estudos Retrospectivos , Estenose Espinal/complicações , Resultado do TratamentoRESUMO
In cervical traumatic spinal cord injury (TSCI), the therapeutic effect of timing of surgery on neurological recovery remains uncertain. Additionally, the relationship between extent of decompression, imaging biomarker evidence of injury severity, and outcome is incompletely understood. We investigated the effect of timing of decompression on long-term neurological outcome in patients with complete spinal cord decompression confirmed on postoperative magnetic resonance imaging (MRI). American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade conversion was determined in 72 AIS grades A, B, and C patients 6 months after confirmed decompression. Thirty-two patients underwent decompressive surgery ultra-early (< 12 h), 25 underwent decompressive surgery early (12-24 h), and 15 underwent decompressive surgery late (> 24-138.5 h) after injury. Age, gender, injury mechanism, intramedullary lesion length (IMLL) on MRI, admission ASIA motor score, and surgical technique were not statistically different among groups. Motor complete patients (p = 0.009) and those with fracture dislocations (p = 0.01) tended to be operated on earlier. Improvement of one grade or more was present in 55.6% of AIS grade A, 60.9% of AIS grade B, and 86.4% of AIS grade C patients. Admission AIS motor score (p = 0.0004) and pre-operative IMLL (p = 0.00001) were the strongest predictors of neurological outcome. AIS grade improvement occurred in 65.6%, 60%, and 80% of patients who underwent decompression ultra-early, early, and late, respectively (p = 0.424). Multiple regression analysis revealed that IMLL was the only significant variable predictive of AIS grade conversion to a better grade (odds ratio, 0.908; confidence interval [CI], 0.862-0.957; p < 0.001). We conclude that in patients with post-operative MRI confirmation of complete decompression following cervical TSCI, pre-operative IMLL, not the timing of surgery, determines long-term neurological outcome.
Assuntos
Medula Cervical/diagnóstico por imagem , Descompressão Cirúrgica/métodos , Imageamento por Ressonância Magnética/métodos , Sociedades Médicas , Traumatismos da Medula Espinal/diagnóstico por imagem , Índices de Gravidade do Trauma , Adulto , Idoso , Medula Cervical/lesões , Medula Cervical/cirurgia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Traumatismos da Medula Espinal/cirurgia , Fatores de Tempo , Estados Unidos , Adulto JovemRESUMO
BACKGROUND: We have previously reported the use of a minimally invasive allograft-filled expandable meshed-bag containment system in the lumbar spine. Subsidence has not been reported with this device. In this retrospective case series, we describe subsidence after lumbar interbody fusion using this device, with 12-month minimum radiographic follow-up. METHODS: Consecutive adult patients that underwent 1- or 2-level interbody fusion with at least 1 year of follow-up were included in this study. Preoperative, postoperative, and final follow-up lumbar radiographs were analyzed to measure disc height at the anterior and posterior margins of the disc space, as well as the neuroforaminal height. RESULTS: Forty-one patients were identified, with a mean age of 63.4 years (± 11.8). A total of 61 levels were treated, with successful fusion observed in 54 levels (88.5%). The mean radiographic follow-up was 24.3 months (± 11.2). The mean disc height pre- and postoperatively was 6.9 mm (± 3.2) and 10.1 mm (± 2.9, P < .001), respectively. The mean disc height at final follow-up was 8.3 mm (± 2.4). Average disc height subsidence was 1.8 mm (± 1.7, P < .001). Overall, average disc height increased by a net 1.3 mm (± 2.5, P < .001). The mean neuroforaminal height pre- and postoperatively was 18.0 mm (± 3.3) and 20.7 mm (± 3.6, P < .001), respectively. The mean neuroforaminal height at final follow-up was 19.2 mm (± 3.4). Average neuroforaminal height subsidence was 1.3 mm (± 3.4, P = .012). Overall, average neuroforaminal height increased by a net 1.7 mm (± 2.8, P = .004). No significant difference in subsidence was observed between 1- and 2-level surgeries. CONCLUSION: An expandable allograft containment system is a feasible alternative for lumbar interbody fusion. Due to its biologic and mechanical nature, the surgeon using such constructs should account for an anticipated average of 18% loss of interbody height due to subsidence during the bony remodeling/fusion process.
RESUMO
Anterior sacral meningoceles (ASMs) are rare lesions often associated with connective tissue disorders. These lesions are typically treated posteriorly via closure of the dural stalk. However, given their insidious nature, ASMs can be quite large on presentation, and this approach may not provide adequate decompression. In this case report, the authors describe the successful treatment of a large ASM through drainage and watertight closure of the cyst with an omental flap. A 43-year-old woman with a history of Marfan syndrome and a large ASM was referred for neurosurgical intervention. The ASM was filling the pelvic cavity and causing severe compression of the bladder. The patient underwent surgical decompression of the cyst through an anterior transabdominal approach and closure of the fistulous tract with a pedicled omental flap. This is the first reported case of successful closure of an ASM with an omental flap. At the 6-month follow-up, the ASM had not recurred on imaging and the patient's symptoms had resolved. Anterior sacral meningoceles are rare lesions that often require neurosurgical intervention. Although most can be treated posteriorly, large ASMs compressing the abdominal or pelvic organs may require a transabdominal approach. Moreover, ASMs with wide dural stalks may benefit from closure with an omental flap.
Assuntos
Síndrome de Marfan/complicações , Meningocele/complicações , Meningocele/cirurgia , Retalhos Cirúrgicos , Adulto , Descompressão Cirúrgica/métodos , Feminino , Humanos , Síndrome de Marfan/diagnóstico por imagem , Meningocele/diagnóstico por imagem , SacroRESUMO
OBJECTIVE The aim of this study was to determine the efficacy of 2 common preoperative surgical skin antiseptic agents, ChloraPrep and Betadine, in the reduction of postoperative surgical site infection (SSI) in spinal surgery procedures. METHODS Two preoperative surgical skin antiseptic agents-ChloraPrep (2% chlorhexidine gluconate and 70% isopropyl alcohol) and Betadine (7.5% povidone-iodine solution)-were prospectively compared across 2 consecutive time periods for all consecutive adult neurosurgical spine patients. The primary end point was the incidence of SSI. RESULTS A total of 6959 consecutive spinal surgery patients were identified from July 1, 2011, through August 31, 2015, with 4495 (64.6%) and 2464 (35.4%) patients treated at facilities 1 and 2, respectively. Sixty-nine (0.992%) SSIs were observed. There was no significant difference in the incidence of infection between patients prepared with Betadine (33 [1.036%] of 3185) and those prepared with ChloraPrep (36 [0.954%] of 3774; p = 0.728). Neither was there a significant difference in the incidence of infection in the patients treated at facility 1 (52 [1.157%] of 4495) versus facility 2 (17 [0.690%] of 2464; p = 0.06). Among the patients with SSI, the most common indication was degenerative disease (48 [69.6%] of 69). Fifty-one (74%) patients with SSI had undergone instrumented fusions in the index operation, and 38 (55%) patients with SSI had undergone revision surgeries. The incidence of SSI for minimally invasive and open surgery was 0.226% (2 of 885 cases) and 1.103% (67 of 6074 cases), respectively. CONCLUSIONS The choice of either ChloraPrep or Betadine for preoperative skin antisepsis in spinal surgery had no significant impact on the incidence of postoperative SSI.
Assuntos
Anti-Infecciosos Locais/uso terapêutico , Clorexidina/análogos & derivados , Povidona-Iodo/uso terapêutico , Coluna Vertebral/cirurgia , Infecção da Ferida Cirúrgica/prevenção & controle , Antissepsia/métodos , Clorexidina/uso terapêutico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Procedimentos Neurocirúrgicos , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos , Infecção da Ferida Cirúrgica/epidemiologia , Resultado do TratamentoRESUMO
OBJECTIVE The objective of this study was to describe the use of a minimally invasive surgical treatment of lumbar spondylolysis in athletes by a fluoroscopically guided direct pars screw placement with recombinant human bone morphogenetic protein-2 (rhBMP-2) and to report on clinical and radiographic outcomes. METHODS A retrospective review was conducted of all patients treated surgically for lumbar spondylolysis via a minimally invasive direct pars repair with cannulated screws. Demographic information, clinical features of presentation, perioperative and intraoperative radiographic imaging, and postoperative data were collected. A 1-cm midline incision was performed for the placement of bilateral pars screws utilizing biplanar fluoroscopy, followed by placement of a fully threaded 4.0-mm-diameter titanium cannulated screw. A tubular table-mounted retractor was utilized for direct pars fracture visualization and debridement through a separate incision. The now-visualized pars fracture could then be decorticated, with care taken not to damage the titanium screw when using a high-speed drill. Local bone obtained from the curettage was then placed in the defect with 1.05 mg rhBMP-2 divided equally between the bilateral pars defects. RESULTS Nine patients were identified (mean age 17.7 ± 3.42 years, range 14-25 years; 6 male and 3 female). All patients had bilateral pars fractures of L-4 (n = 4) or L-5 (n = 5). The mean duration of preoperative symptoms was 17.22 ± 13.2 months (range 9-48 months). The mean operative duration was 189 ± 29 minutes (range 151-228 minutes). The mean intraoperative blood loss was 17.5 ± 10 ml (range 10-30 ml). Radiographic follow-up was available in all cases; the mean length of time from surgery to the most recent imaging study was 30.8 ± 23.3 months (range 3-59 months). The mean hospital length of stay was 1.13 ± 0.35 days (range 1-2 days). There were no intraoperative complications. CONCLUSIONS Lumbar spondylolysis treatment with a minimally invasive direct pars repair is a safe and technically feasible option that minimizes muscle and soft-tissue dissection, which may particularly benefit adolescent patients with a desire to return to a high level of physical activity.
Assuntos
Proteína Morfogenética Óssea 2/administração & dosagem , Parafusos Ósseos , Vértebras Lombares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Espondilólise/cirurgia , Fator de Crescimento Transformador beta/administração & dosagem , Adolescente , Parafusos Ósseos/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Monitorização Neurofisiológica Intraoperatória/métodos , Vértebras Lombares/diagnóstico por imagem , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/instrumentação , Proteínas Recombinantes/administração & dosagem , Estudos Retrospectivos , Espondilólise/diagnóstico por imagem , Adulto JovemRESUMO
We have developed a piglet model to assess chemotherapy administration directly into the fourth ventricle as a potential treatment for medulloblastoma and other malignant posterior fossa tumors. The objective of this study was to assess safety and pharmacokinetics after methotrexate infusions into the fourth ventricle. Catheters were inserted into the fourth ventricle and lumbar cistern in five piglets. Two milligrams of Methotrexate (MTX) was infused into the fourth ventricle on five consecutive days. Safety was assessed by neurological examination, 4.7 T MRI, and post-mortem pathological analysis. MTX levels in serum and cerebrospinal fluid (CSF) were measured, and area under the concentration-time curve (AUC) was calculated for CSF samples. No neurological deficits were caused by MTX infusions. One piglet died from complications of anesthesia induction for MRI scanning. MRI scans showed accurate catheter placement without signal changes in the brainstem or cerebellum. One piglet had asymptomatic ventriculomegaly. Pathological analysis demonstrated meningitis and choroid plexitis consisting predominantly of CD-3 positive T-lymphocytes in all piglets and a small focal area of subependymal necrosis in one. In all piglets, mean peak MTX level in fourth ventricular CSF exceeded that in lumbar CSF by greater than five-fold. Serum MTX levels were undetectable or negligible. Statistically significant differences between fourth ventricle and lumbar AUC were detected at peaks (P = 0.01) and at all collection time points (P = 0.01) but not at troughs (P = 0.36). MTX can be infused into the fourth ventricle without clinical or radiographic evidence of damage. An inflammatory response without clinical correlate is observed. Significantly higher peak MTX levels are observed in the fourth ventricle than in the lumbar cistern.
Assuntos
Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacocinética , Quarto Ventrículo/efeitos dos fármacos , Metotrexato/administração & dosagem , Metotrexato/farmacocinética , Animais , Área Sob a Curva , Contagem de Células/métodos , Inibidores Enzimáticos/sangue , Inibidores Enzimáticos/líquido cefalorraquidiano , Imageamento por Ressonância Magnética/métodos , Metotrexato/sangue , Metotrexato/líquido cefalorraquidiano , Modelos Animais , Suínos , Fatores de TempoRESUMO
We hypothesize that infusion of chemotherapeutic agents directly into the fourth ventricle potentially may play a role in treating malignant posterior fossa brain tumors. Accordingly, we used a piglet model developed in our laboratory to test the safety of etoposide infusions into the fourth ventricle and to study the pharmacokinetics associated with these infusions. In 5 piglets, closed-tip silicone catheters were inserted into the fourth ventricle and lumbar cistern. Five consecutive daily infusions of etoposide (0.5 mg) were administered via the fourth ventricle catheter. Serum and CSF from both catheters were sampled for measurement of etoposide level by reversed-phase high performance liquid chromatography (HPLC). For CSF samples, area under the concentration-time curve (AUC) was calculated. Piglets underwent daily neurological examinations, a 4.7 Tesla MRI scan, and then were sacrificed for post-mortem brain examination. No neurological deficits or signs of meningitis were caused by intraventricular chemotherapy infusions. MRI scans showed catheter placement within the fourth ventricle but no signal changes in the brain stem or cerebellum. In all piglets, the mean fourth ventricular CSF peak etoposide level exceeded the mean peak lumbar etoposide levels by greater than 10-fold. Statistically significant differences between fourth ventricle and lumbar AUC were noted at peaks (DeltaAUC = 3384196 ng h/ml with 95%CI: 1758625, 5009767, P = 0.0044) and at all collection time points (DeltaAUC = 1422977 ng h/ml with 95%CI: 732188, 2113766, P = 0.0046) but not at troughs (DeltaAUC = -29546 ng h/ml (95%CI: -147526, 88434.2, P = 0.5251). Serum etoposide was absent at two and four hours after intraventricular infusions in all animals. Pathological analysis demonstrated meningitis, choroid plexitis, and ependymitis in the fourth and occasionally lateral ventricles. Etoposide can be infused directly into the fourth ventricle without clinical or radiographic evidence of damage. Autopsy examination revealed ventriculitis and meningitis which did not have a clinical correlate. Etoposide does not distribute evenly throughout CSF spaces after administration into the fourth ventricle, and higher peak CSF levels are observed in the fourth ventricle than in the lumbar cistern.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacocinética , Etoposídeo/administração & dosagem , Etoposídeo/farmacocinética , Quarto Ventrículo/efeitos dos fármacos , Neoplasias Infratentoriais/patologia , Animais , Antineoplásicos Fitogênicos/sangue , Antineoplásicos Fitogênicos/líquido cefalorraquidiano , Antineoplásicos Fitogênicos/farmacologia , Área Sob a Curva , Contagem de Células , Cromatografia Líquida de Alta Pressão/métodos , Intervalos de Confiança , Modelos Animais de Doenças , Etoposídeo/sangue , Etoposídeo/líquido cefalorraquidiano , Etoposídeo/farmacologia , Neoplasias Infratentoriais/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Exame Neurológico/métodos , Suínos , Fatores de TempoRESUMO
OBJECT: The authors hypothesized that chemotherapy infusions directly into the fourth ventricle may potentially play a role in treating malignant posterior fossa tumors. In this study the safety and pharmacokinetics of etoposide administration into the fourth ventricle was tested using an indwelling catheter in piglets. METHODS: A closed-tip silicone lumbar drain catheter was inserted into the fourth ventricle via a posterior fossa craniectomy and 5 daily infusions of etoposide (0.5 mg in 5 animals) or normal saline (in 2 animals) were instilled. Piglets (10-18 kg, 2-3 months of age) underwent daily neurological examinations and 4.7-T magnetic resonance (MR) imaging after the final infusion and were then killed for postmortem examination. Pharmacokinetics were studied using reversed-phase high-performance liquid chromatography on cerebrospinal fluid (CSF) samples at 0.25, 1, 2, 4, 8, 12, and 24 hours after etoposide infusion. Peak and trough CSF etoposide levels were measured for each subsequent infusion. Serum etoposide levels were obtained at 2 and 4 hours after infusion. RESULTS: All piglets remained neurologically intact, and MR images demonstrated catheter placement within the fourth ventricle without signal changes in the brainstem or cerebellum. Serum etoposide was absent at 2 and 4 hours after intraventricular infusions. When adequate samples could be obtained for analysis, CSF etoposide levels peaked 15 minutes after infusion and progressively decreased. Cytotoxic levels (> 0.1 microg/ml) were maintained for 5 consecutive peak and trough measurements with 1 exception. Etoposide-related neuropathology included moderate-to-severe T-lymphocytic meningitis and fourth and lateral ventricular choroid plexitis with associated subependymal inflammation. CONCLUSIONS: Etoposide can be infused directly into the fourth ventricle without clinical or imaging evidence of damage. Cytotoxic CSF etoposide levels can be maintained for 24 hours with a single daily infusion into the fourth ventricle using an indwelling catheter. Intraventricular etoposide elicits an inflammatory response, the long-term effects of which are as yet undetermined.