Perioperative nonopioid agents for pain control in spinal surgery.

PURPOSE: Commonly used nonopioid analgesic agents that are incorporated into multimodal perioperative pain management protocols in spinal surgery are reviewed. SUMMARY: Spinal procedures constitute perhaps some of most painful surgical interventions, as they often encompass extensive muscle dissection, tissue retraction, and surgical implants, as well as prolonged operative duration. Perioperative nonopioid analgesics frequently used in multimodal protocols include gabapentin, pregabalin, acetaminophen, dexamethasone, ketamine, and nonsteroidal antiinflammatory drugs (NSAIDs). There is evidence to suggest that gabapentin is safe and effective in reducing opioid consumption and pain scores at optimal doses of 600-900 mg orally administered preoperatively. Pregabalin 150-300 mg orally perioperatively has been shown to reduce both pain and narcotic consumption. Most reports concur that a single 1-g i.v. perioperative dose is safe in adults and that this dose has been shown to reduce pain and attenuate narcotic requirements. Dexamethasone's influence on postoperative pain has primarily been investigated for minor spinal procedures, with limited evidence for spinal fusions. Ketamine added to a patient-controlled analgesia regimen appears to be efficacious for 24 hours postoperatively when implemented for microdiskectomy and laminectomy procedures at doses of 1 mg/mL in a 1:1 mixture with morphine. For patients undergoing laminectomy or diskectomy, NSAIDs appear to be safe and effective in reducing pain scores and decreasing opioid consumption. CONCLUSION: Preemptive analgesic therapy combining nonopioid agents with opioids may reduce narcotic consumption and improve patient satisfaction after spinal surgery. Such therapy should be considered for patients undergoing various spinal procedures in which postoperative pain control has been historically difficult to achieve.

Novel free-hand T1 pedicle screw method: Review of 44 consecutive cases.

SUMMARY OF BACKGROUND DATA: Multilevel posterior cervical instrumented fusions are becoming more prevalent in current practice. Biomechanical characteristics of the cervicothoracic junction may necessitate extending the construct to upper thoracic segments. However, fixation in upper thoracic spine can be technically demanding owing to transitional anatomy while suboptimal placement facilitates vascular and neurologic complications. Thoracic instrumentation methods include free-hand, fluoroscopic guidance, and CT-based image guidance. However, fluoroscopy of upper thoracic spine is challenging secondary to vertebral geometry and patient positioning, while image-guided systems present substantial financial commitment and are not readily available at most centers. Additionally, imaging modalities increase radiation exposure to the patient and surgeon while potentially lengthening surgical time. MATERIALS AND METHODS: Retrospective review of 44 consecutive patients undergoing a cervicothoracic fusion by a single surgeon using the novel free-hand T1 pedicle screw technique between June 2009 and November 2012. A starting point medial and cephalad to classic entry as well as new trajectory were utilized. No imaging modalities were employed during screw insertion. Postoperative CT scans were obtained on day 1. Screw accuracy was independently evaluated according to the Heary classification. RESULTS: In total, 87 pedicle screws placed were at T1. Grade 1 placement occurred in 72 (82.8%) screws, Grade 2 in 4 (4.6%) screws and Grade 3 in 9 (10.3%) screws. All Grade 2 and 3 breaches were <2 mm except one Grade 3 screw breaching 2-4 mm laterally. Only two screws (2.3%) were noted to be Grade 4, both breaching medially by less than 2 mm. No new neurological deficits or returns to operating room took place postoperatively. CONCLUSIONS: This modification of the traditional starting point and trajectory at T1 is safe and effective. It attenuates additional bone removal or imaging modalities while maintaining a high rate of successful screw placement compared to historical controls.

Thoracolumbar instrumentation with CT-guided navigation (O-arm) in 270 consecutive patients: accuracy rates and lessons learned.

OBJECT: Thoracolumbar instrumentation has experienced a dramatic increase in utilization over the last 2 decades. However, pedicle screw fixation remains a challenging undertaking, with suboptimal placement contributing to postoperative pain, neurological deficit, vascular complications, and return to the operating suite. Image-guided spinal surgery has substantially improved the accuracy rates for these procedures. However, it is not without technical challenges and a learning curve for novice operators. The authors present their experience with the O-arm intraoperative imaging system and share the lessons they learned over nearly 5 years. METHODS: The authors performed a retrospective chart review of 270 consecutive patients who underwent thoracolumbar pedicle screw fixation utilizing the O-arm imaging system in conjunction with StealthStation navigation between April 2009 and September 2013 at a single tertiary care center; 266 of the patients underwent CT scanning on postoperative Day 1 to evaluate hardware placement. The CT scans were interpreted prospectively by 3 neuroradiologists as part of standard work flow and retrospectively by 2 neurosurgeons and a senior resident. Pedicle screws were evaluated for breaches according to the 3-tier classification proposed by Mirza et al. RESULTS: Of 270 patients, 266 (98.5%) were included in the final analysis based on the presence of a postoperative CT scan. Overall, 1651 pedicle screws were placed in 266 patients and yielded a 5.3% breach rate; 213 thoracic and 1438 lumbosacral pedicle screws were inserted with 6.6% and 5.1% breach rates, respectively. Of the 87 suboptimally placed screws, there were 13 Grade 1, 16 Grade 2, and 12 Grade 3 misses as well as 46 anterolateral or "tip-out" perforations at L-5. Four patients (1.5%) required a return to the operating room for pedicle screw revision, 2 of whom experienced transient radicular symptoms and 2 remained asymptomatic. Interestingly, the pedicle breach rate was higher than anticipated at 13.21% for the 30 patients over the initial 6-month period with the O-arm. After certain modifications to the authors' technique, the subsequent 30 patients experienced a statistically significant decrease in breach rate at 5.6% (p = 0.014). CONCLUSIONS: Image-guided spinal surgery can be a great option in the operating room and provides high pedicle screw accuracy rates. With numerous systems commercially available, it is important to develop a systematic approach regardless of the technology in question. There is a learning curve for surgeons unfamiliar with image guidance that should be recognized and appreciated when transitioning to navigation-assisted spinal surgery. In fact, the authors' experience with a large patient cohort suggests that this learning curve may be more significant than previously reported.

Sinovenous thrombosis associated with skull fracture in the setting of blunt head trauma.

BACKGROUND: Emerging literature suggests that closed head injuries may be an important etiology of cerebral venous sinus thrombosis (CVST). Fractures over the dural sinuses, in particular, may predispose such patients to this secondary complication. The purpose of this study was to determine the incidence and characteristics of CVST resulting from skull fractures overlying cerebral venous sinuses at a single tertiary care center. METHODS: A retrospective review of consecutive patients presenting to our institution with skull fractures from blunt head trauma between 1 January 2009 and 31 December 2011 who underwent either a computed tomography (CT) or magnetic resonance (MR) venogram. Patient demographics, associated intracranial injuries, admission Glasgow Coma Scale (GCS), presence of CVST, and post-hospital disposition were recorded. RESULTS: Overall, 908 patients with skull fractures presented to the institution. Of those, 63 had fractures over a sinus and a venogram satisfying inclusion criteria. Twenty-two (34.9 %) patients demonstrated a thrombus in at least one sinus. There was no statistical difference in patient demographics, presenting GCS, length of stay (LOS), or outcome between patients with or without a thrombus. Pediatric patients had significantly shorter LOS (11 vs. 4 days, p < 0.01) compared to adults. Adults had a greater incidence of total sinus occlusions while children had more non-occlusive thrombus formations; both were statistically significant (p = 0.035 and p = 0.037, respectively). CONCLUSIONS: This report suggests that over 10 % of skull fractures involve cerebral venous sinuses, thus emphasizing the need to rule out CVST in patients suffering blunt head trauma. We propose including a venogram as part of the initial trauma work-up for these patients. Moreover, our data suggest that pediatric patients may be predisposed to less severe injuries than their adult counterparts.

Metastatic brain tumors: current therapeutic options and historical perspective.

Metastatic brain tumors affect more than 150,000 patients annually in the United States. The therapeutic paradigms for these tumors have evolved over the years and currently encompass numerous modalities implemented by treating physicians across several medical disciplines. The armamentarium of brain tumor treatment involves neurosurgical intervention, whole-brain and focused radiation modalities, chemotherapy, and immunotherapy. Patient selection, however, remains critical to achieve maximal therapeutic benefit and depends on functional status, number and location of lesions, and tissue histologic findings. Best outcomes can be expected with a multidisciplinary approach to patient care where state-of-the-art treatment options are readily available.

Effects of tribromoethanol-medetomidine combination on cycling and ovariectomized Sprague-Dawley rats.

Although commonly used to induce anesthesia in rodents, the effective dose of tribromoethanol is associated with various side effects. The authors previously found that a tribromoethanol-medetomidine combination reduced the dose of tribromoethanol necessary for effective anesthesia in male Sprague-Dawley rats, an effect reversible by atipamezole. Here, the authors focus on the effect of this anesthetic combination in female Sprague-Dawley rats, its effects on their estrous cycles, and its efficacy at low sex hormone levels. Their results suggest that the anesthetic combination is effective in female rats, does not affect their estrous cycles, and works even when hormone levels are low, such as after ovariectomy.

Transplantation of embryonic stem cells overexpressing Bcl-2 promotes functional recovery after transient cerebral ischemia.

The study tested the hypothesis that transplantation of embryonic stem (ES) cells into rat cortex after a severe focal ischemia would promote structural repair and functional recovery. Overexpression of the human anti-apoptotic gene bcl-2 in ES cells was tested for increasing survival and differentiation of transplanted cells and promoting functional benefits. Mouse ES cells, pretreated with retinoic acid to induce differentiation down neural lineages, were transplanted into the post-infarct brain cavity of adult rats 7 days after 2-h occlusion of the middle cerebral artery (MCA). Over 1-8 weeks after transplantation, the lesion cavity filled with ES cell-derived cells that expressed markers for neurons, astrocytes, oligodendrocytes, and endothelial cells. ES cell-derived neurons exhibited dendrite outgrowth and formed a neuropil. ES cell-transplanted animals exhibited enhanced functional recovery on neurological and behavioral tests, compared to control animals injected with adult mouse cortical cells or vehicle. Furthermore, transplantation with ES cells overexpressing Bcl-2 further increased the survival of transplanted ES cells, neuronal differentiation, and functional outcome. This study supports that ES cell transplantation and gene modification may have values for enhancing recovery after stroke.

Estradiol stimulates gene expression of norepinephrine biosynthetic enzymes in rat locus coeruleus.

Gender-specific differences in susceptibility to a number of disorders related to catecholaminergic systems, including depression and hypertension, have been postulated to be mediated, at least in part, by estrogens. In this study, we examined if estrogens may regulate gene expression of norepinephrine biosynthetic enzymes. Administration of five injections of 15 or 40 microg/kg estradiol benzoate to ovariectomized (OVX) female rats elicited a dose-dependent elevation in mRNA levels of tyrosine hydroxylase (TH) in locus coeruleus, to as great as 3-fold over control. Dopamine beta-hydroxylase (DBH) mRNA levels were also similarly increased. To examine the mechanism, PC12 cells were cotransfected with luciferase reporter constructs under control of DBH or TH promoters [pDBH/Luc(-2,236/+21) or pTH/Luc(-272/+27 or -773/+27)] with an expression vector for estradiol receptor alpha. The cells were treated with 17beta-estradiol (E(2)) for 12-36 h. E(2) triggered a several fold increase in luciferase activity under control of the DBH promoter in a dose-dependent fashion. Omission of estrogen receptor alpha or addition of the estrogen receptor antagonist ICI 182,780 prevented the DBH promoter-driven increase in luciferase. When E(2) was given with 0.2 mM CPT-cAMP, reporter activity with pDBH/Luc(-2,236/+21) was increased greater than with either treatment alone. In contrast, addition of E(2) to cells transfected with pTH/Luc(-272/+27) elicited no change in basal luciferase activity nor in the response to 0.2 mM CPT-cAMP. These findings are the first to reveal that estrogen can stimulate DBH gene expression. Differing mechanisms may underlie the regulation of TH and DBH gene expression by estrogens.