Effects of Intrathecal Morphine Administration in Patients Undergoing Primary Total Hip Arthroplasty Under Spinal Anesthesia With Quadratus Lumborum Block for Postoperative Analgesia.

Introduction Quadratus lumborum (QL) block has previously been shown to provide improved analgesia in patients undergoing primary total hip arthroplasty (THA) under spinal anesthesia when compared to spinal anesthesia alone. Additionally, recent studies have shown the addition of intrathecal morphine (ITM) to provide superior postoperative analgesia in patients undergoing various surgical interventions including total knee arthroplasty under spinal anesthesia with peripheral nerve blockade. At this time, however, there has not been a study evaluating the effects of intrathecal morphine in patients undergoing THA under spinal anesthesia with QL block. This study aims to assess if the addition of intrathecal morphine can provide adequate or even superior postoperative analgesia in patients undergoing primary THA. Methods This retrospective study included 26 patients in the spinal/QL block/intrathecal morphine (SA+QLB+ITM) group, 31 patients in the spinal/QL block group (SA+QLB), and 28 patients in the spinal only (SA or control) group. Twenty-six patients undergoing primary THA under a combination of spinal anesthesia and peripheral nerve blockade (quadratus lumborum block) were given a dose of 100 mcg of intrathecal morphine. Various parameters were evaluated including Post-Anesthesia Care Unit (PACU) and 24-hour visual analog scale (VAS) scores, time to first opioid use, 24- and 48-hour total opioid use as oral morphine equivalents (OME), 24-hour ambulation distance, and time from block placement to hospital discharge. The results were analyzed and compared to patients undergoing primary THA under spinal anesthesia with QL block (no intrathecal morphine) and compared to a control group of patients undergoing primary THA under spinal anesthesia only. Results The study analysis included 26 patients in the SA+QLB+ITM group, 31 patients in the SA+QLB group, and 28 patients in the SA (control) group. When compared with the control group, the SA+QLB+ITM had lower 24-hour total opioid usage (mean difference 20.80 OME, CI 6.454 to 35.15, p-value 0.0025), longer time to 1st opioid use (mean difference -20.51 hours later, p-value .0052), lower 24-hr VAS (difference 2.421, p-value 0.0012, CI 0.8559 to 3.987), and faster time to discharge (16.00 hr earlier, p-value 0.0459). When compared to the SA+QLB group, the SA+QLB+ITM group only showed a statistically significant difference in faster time to discharge (19.46 hr earlier, p-value 0.0068). However, while there was no statistically significant difference in time to 1st opioid use between the control and SA+QLB group, the difference did become significant when comparing the control to the SA+QLB+ITM group (mean difference -20.51 hours later (p-value .0052). There was no significant difference in either of the three groups in ambulation distance at 24 hours, PACU VAS, or 48-hour total opioid use. Conclusion Our study concludes that the addition of 100 mcg ITM for total hip arthroplasty under spinal anesthesia improved postoperative analgesia compared to the control group. Also, the ITM group did better with respect to delay in first opioid use and decreased hospital stay compared to the control and block-only groups. Our study warrants no more concerns of PONV, pruritus, or respiratory depression with this dose of ITM and requires standard postoperative care.

The Dose Comparison of Intrathecal Morphine for Postoperative Analgesia in Total Knee Arthroplasty Under Spinal Anesthesia: A Single Institute Retrospective Study.

Background and purpose of the study Intrathecal morphine (ITM) provides effective postoperative analgesia in patients undergoing total knee arthroplasty (TKA) under spinal anesthesia. However, the ideal dose at which maximal analgesic effects can be delivered with minimal side effects is not clearly known. This retrospective study is aimed to compare two different doses of ITM with respect to analgesia benefits and side effects. Methods This is a retrospective, descriptive, single-center study approved by the Institutional Review Board (IRB) at the University of Alabama at Birmingham. Three patient groups were selected: a control group receiving continuous adductor canal block (CCACB) under spinal anesthesia, and two experimental groups receiving single-dose adductor canal block (SSACB) under spinal anesthesia with either 100 mcg or 150 mcg of ITM. The sample size included 75 patients (25 per group) who were 18 years and older, American Society of Anesthesiology (ASA) class 1-3 who were undergoing primary TKA. Patients with chronic pain or opioid use exceeding 30 days and those undergoing surgeries other than primary TKA were excluded. Outcome data, including opioid use (from which post-operative oral morphine equivalents (OME) were calculated), antiemetic use, visual analog pain scale (VAS) scores, distance ambulated at 24 hours, and length of hospital stay, were extracted by chart review. Results In the post-anesthesia care unit (PACU), patients in both ITM groups experienced significantly lower opioid consumption and pain scores compared to the control group (p<.001). Furthermore, cumulative OME at 24 hours was significantly less in the ITM groups compared to the control, but there was no difference between ITM doses (p=0.004; mean cumulative OME for control was 77.2 OME vs 43.4 OME for 100 mcg ITM vs 42.6 OME for 150 mcg ITM). Antiemetic usage did not increase in the ITM groups. Although there was no statistically significant difference in ambulation at 24 hours, both ITM groups exhibited a trend toward greater average ambulation distance compared to the control group (p=0.095; mean distance walked for control was 67.6 feet, 76.6 feet for 100 mcg ITM vs 98.8 feet for 150 mcg ITM). Hospital length of stay did not significantly differ between the groups. Conclusion ITM doses of 100 mcg and 150 mcg provide effective analgesia for patients undergoing lower extremity total knee arthroplasty under spinal anesthesia. Patients receiving ITM had better pain scores in the immediate post-operative period and had overall less oral morphine equivalent consumption when compared to control. In addition, the safety and side effect profile for ITM is similar for both doses as there was no incidence of respiratory depression and antiemetic usage did not differ between all study arms. Future studies should explore the use of higher ITM doses and consider a broader patient population to further understand the advantages and potential drawbacks of ITM in TKA surgery.

Effects of Intraoperative Ketamine on Post-Operative Recovery in Obstructive Sleep Apnea Patients: A Case-Control Study.

Objective To evaluate the post-operative outcomes of patients with obstructive sleep apnea (OSA) given intraoperative ketamine. Design: case-control study A total of 574 patients (287 received ketamine and 287 were matched controls) diagnosed with OSA and body mass index (BMI) > 30 who received general anesthesia were included in this study. Patients given intraoperative ketamine were matched (1:1) with those who did not receive ketamine for age, gender, BMI, ethnicity, anesthesia time, intraoperative fentanyl dose, ketamine dose, and surgery type. A sub-analysis was performed based on the dose of ketamine administered and also on the surgery type. Measured outcomes include post-operative pain scores, post-operative opioid requirements, respiratory status, oxygen use, and duration post-operatively. Results Intraoperative ketamine use did not decrease pain scores or post-operative opioid use when compared with the control (no intraoperative ketamine) group. Patients who received high-dose ketamine had significantly higher post-operative pain scores (p=0.048) while in the post-anesthesia care unit (PACU) and required supplemental oxygen for a longer period of time (p = 0.030), pain scores were not significant for patients who underwent orthopedic/spine procedures (p = 0.074), and high-dose ketamine group patients who underwent orthopedic/spine surgery required significantly more opioids in the PACU (p = 0.031). Among patients who received low-dose ketamine, those who underwent head, ear, nose, and throat surgery required significantly more opioids in PACU (p = 0.022). Conclusions Low-dose intraoperative ketamine did not decrease pain scores or post-operative opioid use significantly and did not improve standard respiratory recovery parameters for OSA patients after surgery. Neither low- nor high-dose ketamine demonstrated the anticipated benefits of low pain scores and reduced post-operative opioid use. These outcomes will differ depending on the surgery type and dose of ketamine used.

T1 Erector Spinae Plane Block Catheter As a Novel Treatment Modality for Pancoast Tumor Pain.

Pancoast tumors are non-small cell lung tumors, which can invade the ribs, vertebrae, sympathetic ganglia and brachial plexus. In this study, a patient with right-sided Pancoast tumor presented with intractable chronic pain on the right neck, upper extremity and chest wall. The chronic pain associated with Pancoast tumor, which was difficult to treat with opioids and other medications, was effectively treated with a high-thoracic erector spinae plane block (ESPB). Prolonged analgesia was provided with an ESP catheter to wean the patient from opioids. This case report provides an example where the novel interfacial ESP block can provide pain relief in challenging situations such as lung malignancies involving deeper structures and extensive areas of pain.

The efficacy and safety of pain management before and after implementation of hospital-wide pain management standards: is patient safety compromised by treatment based solely on numerical pain ratings?

UNLABELLED: Inadequate analgesia in hospitalized patients prompted the Joint Commission on Accreditation of Healthcare Organizations in 2001 to introduce standards that require pain assessment and treatment. In response, many institutions implemented treatment guided by patient reports of pain intensity indexed with a numerical scale. Patient safety associated with treatment of pain guided by a numerical pain treatment algorithm (NPTA) has not been examined. We reviewed patient satisfaction with pain control and opioid-related adverse drug reactions before and after implementation of our NPTA. Patient satisfaction with pain management, measured on a 1-5 scale, significantly improved from 4.13 to 4.38 (P < 0.001) after implementation of an NPTA. The incidence of opioid over sedation adverse drug reactions per 100,000 inpatient hospital days increased from 11.0 pre-NPTA to 24.5 post-NPTA (P < 0.001). Of these patients, 94% had a documented decrease in their level of consciousness preceding the event. Although there was an improvement in patient satisfaction, we experienced a more than two-fold increase in the incidence of opioid over sedation adverse drug reactions in our hospital after the implementation of NPTA. Most adverse drug reactions were preceded by a documented decrease in the patient's level of consciousness, which emphasizes the importance of clinical assessment in managing pain. IMPLICATIONS: Although patient satisfaction with pain management has significantly improved since the adoption of pain management standards, adverse drug reactions have more than doubled. For the treatment of pain to be safe and effective, we must consider more than just a one-dimensional numerical assessment of pain.

Modulation of renal glomerular disease using remote delivery of adenoviral-encoded solubletype II TGF-beta receptor fusion molecule.

BACKGROUND: Systemic adenoviral (Ad) gene therapy for renal disorders is largely hampered by the unique architecture of the kidney. Consequently, currently available Ad vectors are of only limited therapeutic utility in the context of glomerular and fibroproliferative renal diseases. METHODS: The Ad vectors studied in the context of blocking renal fibrosis were AdTbeta-ExR and AdCATbeta-TR. AdTbeta-ExR encodes a chimeric soluble molecule comprising the entire ectodomain of the human type II TGF-beta receptor, genetically fused to the Fc fragment of the human IgG1 (sTbetaRII), while AdCATbeta-TR encodes only the dominant-negative truncated ectodomain of the human type II TGF-beta receptor. The biologic activity of the type II TGF-beta receptor was evaluated in vitro by its ability to inhibit cellular proliferation and in vivo in a unilateral ureter obstruction fibrosis model. Renal targeting with sTbetaRII was evaluated immunohistochemically after intramuscular (IM) delivery of AdTbeta-ExR. The renal antifibrotic effect of the Ad vectors was evaluated in a lupus murine model with both light and electron microscopy and urinalysis. RESULTS: sTbetaRII was detected in the glomeruli after remote IM injection of AdTbeta-ExR, but not the control AdCATbeta-TR, indicating renal deposition of the heterologous soluble fusion protein after its expression in the muscle and secretion into the circulation. AdTbeta-ExR, but not AdCATbeta-TR, could transiently inhibit mesangial expansion, glomerular hypercellularity, proteinuria and cortical interstitial fibrosis in a murine lupus model. However, the autoimmune renal disease eventually surpassed the antifibrotic effect. CONCLUSIONS: These results indicate the superiority of a soluble type II TGF-beta receptor over a dominant-negative, non-soluble type II TGF-beta receptor in the context of blocking renal fibrosis in murine models.

Development of a therapeutic adenoviral vector for cholangiocarcinoma combining tumor-restricted gene expression and infectivity enhancement.

Cholangiocarcinoma is an invasive malignancy that is most often unresectable upon diagnosis and unresponsive to chemotherapy and radiation. While adenoviral gene therapy has shown promise in treating many tumors, systemic toxicity and low tumor transduction efficiency have hampered its application in many gastrointestinal cancers. To overcome these difficulties, we have constructed an adenoviral vector utilizing a tumor-specific promoter (TSP) for selective transgene expression and a vector with an RGD-motif in the fiber-knob region for infectivity enhancement. In seeking a TSP for cholangiocarcinoma, Secretory Leukoprotease Inhibitor, Midkine, Gastrin Releasing Peptide, VEGF, Cox-2M, and Cox-2L promoters were configures in adenoviral vectors, and evaluated in cholangiocarcinoma cells lines (Oz and SkChA-1). Luciferase assays demonstrated that Cox-2 promoters (M and L) showed the highest promoter activity, with Cox-2M appearing slightly stronger than Cox-2L. Infectivity enhanced vectors with RGD-motif in the fiber-knob region were also constructed with the luciferase transgene driven by a CMV control and the Cox-2M and Cox-2L promoters. Subsequent luciferase assays comparing the unmodified vectors to the RGD-modified versions demonstrated higher levels of luciferase activity than the RGD-infected cells. This paradigm was then applied to a therapeutic HSV-TK/GCV model by constructing RGD-enhanced HSV-TK vectors driven by Cox-2M and Cox-2L promoters. In vitro cytocidal effect analysis confirmed that the RGD-modified, cox-2 (M and L) driven vectors showed a stronger cytocidal effect upon gancyclovir administration than the vectors with wild-type fiber. The Cox-2 promoter demonstrates a favorable selectivity profile for cholangiocarcinoma, and RGD-modification further enhances transduction efficiency. This combination has potential to overcome the obstacles to clinical application of adenoviral gene therapy in cholangiocarcinoma.

Adenoviral gene therapy for renal cancer requires retargeting to alternative cellular receptors.

Metastatic renal cell carcinoma (RCC) is one of the most treatment-resistant malignancies in humans. Therefore, the identification of new agents with better antitumor activity merits a high priority in the treatment of advanced RCC. In this regard, gene therapy with adenoviral (Ad) vectors is a promising new modality for cancer. However, a primary limiting factor for the use of Ad vectors for cancer gene therapy is their critical dependence on cellular expression of the primary Ad receptor, the coxsackie and adenovirus receptor (CAR), known to be down-regulated in many cancer types. Following the identification of CAR deficiency in RCC lines, we have found abundant membrane expression of alpha(v)beta 3 and alpha(v)beta 5 integrins and of the putative receptor to Ad serotype 3 (Ad3). As an alternative gene therapy approach for RCC that would circumvent CAR deficiency, we employed retargeting of replication-incompetent Ad vectors and replication-competent Ad viruses to alpha(v)beta 3 and alpha(v)beta 5 integrins and to the putative Ad3 receptor. These strategies to genetically alter Ad tropism were based on either the insertion of a cysteine-aspartate-cysteine-arginine-glycine-aspartate-cysteine-phenylalanine-cysteine (RGD) motif into the HI loop of the Ad fiber knob domain or on generation of a chimeric Ad fiber composed of adenovirus serotype 5 shaft/Ad3 knob. Both strategies proved highly efficient to circumvent CAR deficiency and enhance gene delivery into RCC cells. Furthermore, in the context of replication-competent Ad, tropism alteration resulted in distinct capacity of the retargeted viruses to infect, replicate, and lyse RCC models in vitro and in vivo. The retargeting strategies were particularly beneficial in the context of replication-competent Ad. These findings underscore the importance of CAR-independent cellular entry mechanisms in RCC and are highly consequential for the development of viral antitumor agents for RCC and other CAR-negative tumors.