Three Newly Approved Analgesics: An Update

Since 2008, three new analgesic entities, tapentadol immediate release (Nucynta) diclofenac potassium soft gelatin capsules (Zipsor), and bupivacaine liposome injectable suspension (EXPAREL) were granted US Food and Drug Administration (FDA) approval to treat acute pain. Tapentadol immediate-release is a both a mu-opioid agonist and a norepinephrine reuptake inhibitor, and is indicated for the treatment of moderate to severe pain. Diclofenac potassium soft gelatin capsules are a novel formulation of diclofenac potassium, which is a nonsteroidal anti-inflammatory drug (NSAID), and its putative mechanism of action is through inhibition of cyclooxygenase enzymes. This novel formulation of diclofenac allows for improved absorption at lower doses. Liposomal bupivacaine is a new formulation of bupivacaine intended for single-dose infiltration at the surgical site for postoperative analgesia. Bupivacaine is slowly released from this liposomal vehicle and can provide prolonged analgesia at the surgical site. By utilizing NSAIDs and local anesthetics to decrease the transmission of afferent pain signals, less opioid analgesics are needed to achieve analgesia. Since drug-related adverse events are frequently dose related, lower doses from different drug classes may be employed to reduce the incidence of adverse effects, while producing synergistic analgesia as part of a multimodal analgesic approach to acute pain.Key Words: Liposomal bupivacaine, Tapentadol, Diclofenac potassium soft gelatin capsules, AnalgesicsPain, as defined by the International Association for the Study of Pain, is “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”¹ Although there is a subjective and perhaps emotional component to pain, acute pain is usually proportional to the degree of tissue damage.²Pain may serve a protective mechanism to the individual by signaling tissue injury or organ dysfunction that may otherwise result in illness if left unnoticed and untreated. However, pain that is secondary to a surgical intervention is undesirable. Postoperative pain can result in increased sympathetic nervous system activity, guarded breathing, increased likelihood of thrombi formation, and delayed recovery.³ The benefits of adequate postoperative analgesia include improved respiratory, cardiovascular, and gastrointestinal function, improved arterial graft survival, and decreased incidence of thrombotic or septic complications. Not only does adequate postoperative analgesia result in earlier return to function, more rapid patient mobilization, improved healing, reduced health care costs, and improved patient satisfaction, but it may play a role in preventing the progression of chronic pain.^4–6Opioids have traditionally been the most common analgesic for treating moderate to severe postoperative pain.² However, their utility is hampered by undesirable side effects, which are sometimes intolerable to the patient. These side effects include central nervous depression, respiratory depression, pruritus, nausea, vomiting, ileus, tolerance, and opioid-induced hyperalgesia.^4–6 By treating pain with several modalities, including local anesthetics and nonsteroidal anti-inflammatory drugs (NSAIDs,) lower doses of opioids are needed to achieve analgesia while reducing or eliminating opioid-mediated adverse effects.^4,5The multimodal approach to analgesia intervenes pharmacologically at many different inputs along the pain pathway. The synergistic analgesia achieved by affecting pain transmission at multiple points also results in lower doses of each drug administered. Adverse drug reactions or drug toxicities are dose-dependent, so there are fewer side effects from each drug class. This article presents and reviews 3 new analgesic agents that may be useful in treating postoperative dental and maxillofacial pain: tapentadol immediate release (Nucynta) diclofenac potassium soft gelatin capsules (Zipsor) and bupivacaine liposome injectable suspension (EXPAREL).     

When Do Readmissions for Infection Occur After Spine and Total Joint Procedures?

Background

The episode-of-care concept promulgated by the federal government requires hospitals to assume the cost burden for all care rendered up to 30 days after discharge, including all readmissions occurring in that time. Although surgical site infections (SSIs) are a leading cause of readmission after total joint arthroplasties (TJA) and spine surgery, it is unclear whether these readmissions occur relative to the 30-day period.

Questions/Purposes

We determined whether (1) most readmissions for SSIs occurred in 30 days, (2) the type of procedure performed affected the timing of readmission, and (3) the type of infecting organism influenced the timing of readmission.

Methods

From our hospital database we identified 91 patients treated with elective TJAs and spine surgery from 2007 through 2010 who were readmitted with SSIs. Of the 91 patients, 46 had undergone spine surgery and 45 had TJAs. For each of these readmissions, we determined the type of surgery, the length of time from initial discharge to readmission, and the type of infecting organism.

Results

Readmissions after spine surgery were more likely to occur within 30 days of discharge (80.4% for spine, 58.3% for TJAs). In the TJA cohort, there was a trend toward readmissions occurring within 30 days of discharge more often in the THA subset. We identified no correlation between type of infecting organism and timing of readmission.

Conclusions

With the episode-of-care model, SSIs pose a substantial cost burden for hospitals since the majority would be included in the 30-day period included in the bundled reimbursement.     

ASPIRE registry: assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre

Pulmonary hypertension (PH) is a heterogeneous condition. To date, no registry data exists reflecting the spectrum of disease across the five diagnostic groups encountered in a specialist referral centre. Data was retrieved for consecutive, treatment-na?ve cases diagnosed between 2001 and 2010 using a catheter-based approach. 1,344 patients were enrolled, with a mean follow-up of 2.9 yrs. The 3-yr survival was 68% for pulmonary arterial hypertension (PAH), 73% for PH associated with left heart disease, 44% for PH associated with lung disease (PH-lung), 71% for chronic thromboembolic PH (CTEPH) and 59% for miscellaneous PH. Compared with PAH, survival was inferior in PH-lung and superior in CTEPH (p<0.05). Multivariate analysis demonstrated that diagnostic group independently predicted survival. Within PAH, Eisenmenger's survival was superior to idiopathic PAH, which was superior to PAH associated with systemic sclerosis (p<0.005). Within PH-lung, 3-yr survival in sleep disorders/alveolar hypoventilation (90%) was superior to PH-lung with chronic obstructive pulmonary disease (41%) and interstitial lung disease (16%) (p<0.05). In CTEPH, long-term survival was best in patients with surgically accessible disease undergoing pulmonary endarterectomy. In this large registry of consecutive, treatment-na?ve patients identified at a specialist PH centre, outcomes and characteristics differed between and within PH groups. The current system of classification of PH has prognostic value even when adjusted for age and disease severity, emphasising the importance of systematic evaluation and precise classification.     

Living well with medical comorbidities: a biopsychosocial perspective

Objectives. We take a biopsychosocial perspective on age-related diseases by examining psychological correlates of having multiple chronic conditions and determining whether positive psychological functioning predicts advantageous profiles of biological risk factors. Method. Respondents to the national survey of Midlife in the United States who participated in clinical assessments of health and biological processes (n = 998) provided information on chronic medical conditions and multiple domains of psychological functioning. Serum concentrations of interleukin-6 (IL-6) and C-reactive protein (CRP) were determined from fasting blood samples. RESULTS: Life satisfaction declined with increasing comorbidity while negative affect increased. In contrast, positive affect, purpose in life, and positive relations with others were unrelated to comorbidity status. Significant interactions showed that although IL-6 and CRP increased with increasing number of chronic conditions, respondents with higher levels of purpose in life, positive relations with others, and (in the case of CRP) positive affect had lower levels of inflammation compared with those with lower well-being scores. Discussion. The results suggest that many older adults with medical comorbidities maintain high levels of positive psychological functioning that are in turn linked to better profiles of biological disease risk.     

Inverse relationship between cirrhosis and massive tumours in hepatocellular carcinoma

Background

A subset of patients with hepatocellular carcinoma (HCC) present with massive tumours. It is unknown why certain patients develop these massive tumours, and whether this presentation is specific to the underlying viral aetiology or patient demographics such as gender, race and age.

Methods

All patients with HCC at Bellevue Hospital Center, New York from 1998 to 2012 were identified and relevant demographic and clinical information was collected. Computed tomography/magnetic resonance imaging (CT/MRI) images were reviewed and the maximal tumour diameter on axial sections was recorded. Cirrhosis was defined histologically or by radiographical criteria. The two cohorts of massive and non-massive HCC were compared.

Results

A total of 361 patients with HCC were identified, of which 58 were categorized as having a massive HCC using a 13 cm size cut-off. Univariate and multivariate analysis demonstrated a significant association of massive HCC with age <40 years; hepatitis B or Asian ethnicity; and a lack of cirrhosis or platelet count >100.

Discussion

Massive HCC represents a tumour subtype that is associated with young, chronic hepatitis B carriers with non-cirrhotic livers. The clinical implications of this finding are that patients with massive HCC are typically excellent resection candidates barring the presence of gross vascular invasion or distant metastases.     

The safety of a pancreaticoduodenectomy in patients older than 80 years: risk vs. benefits

Background: A pancreaticoduodenectomy (PD) offers the only chance of a cure for pancreatic cancer and can be performed with low mortality and morbidity. However, little is known about outcomes of a PD in octogenarians. Methods: Differences in two groups of patients (Group Y, <80 and Group O, ≥80 year-old) who underwent a PD for pancreatic adenocarcinoma were analysed. Study end-points were length of post-operative stay, overall morbidity, 30-day mortality and overall survival. Results: There were 175 patients in Group Y (mean age 64 years) and 25 patients in Group O (mean age 83 years). Octogenarians had worse Eastern Cooperative Oncology Group (ECOG) Performance Status (PS ≥1: 90% vs. 51%) and American Society of Anesthesiology (ASA) score (>2: 71% vs. 47%). The two groups were similar in underlying co-morbidities, operative time, rates of portal vein resection, intra-operative complications, blood loss, pathological stage and status of resection margins. Octogenarians had a longer post-operative stay (20 vs. 14 days) and higher overall morbidity (68% vs. 44%). There was a single death in each group. At a median follow-up of 13 months median survival appeared similar in the two groups (17 vs. 13 months). Conclusions: As 30-day mortality and survival are similar to those observed in younger patients, a PD can be offered to carefully selected octogenarians.     

The differential effect of BMI on prosthetic versus autogenous breast reconstruction: A multivariate analysis of 12,986 patients

BackgroundThe comparative safety of breast reconstruction in obese patients remains to be clearly defined. This study utilized multi-institutional data to characterize the effect of body mass index (BMI) on breast reconstruction outcomes.MethodsUtilizing Current Procedural Terminology (CPT) codes, patients undergoing tissue expander, pedicled transverse rectus abdominis myocutaneous (TRAM) flap, latissimus dorsi flap, and free flap breast reconstruction were identified in the National Surgical Quality Improvement Program (NSQIP) database. Patients were stratified as obese (BMI ≥ 30) and non-obese (BMI < 30). Overall postoperative morbidity, flap complications, non-flap complications, and reoperation rates were compared among the groups.ResultsOf 12,986 patients who underwent breast reconstruction, 3636 (28.0%) were obese. Overall morbidity was significantly elevated in obese patients across all forms of reconstruction (p < 0.05). BMI was correlated with increased surgical complications for tissue expander, pedicled TRAM, and free flap reconstructions (OR = 1.09, OR = 1.05, OR = 1.10, respectively; p < 0.05). Medical complications were higher in obese patients undergoing tissue expander and pedicled TRAM reconstructions (p = 0.001 and p < 0.001), but no significant difference was observed in latissimus and free flap reconstruction patients. Compared with obese tissue expander recipients, obese patients reconstructed using autologous tissue had higher rates of reoperations (12.8% versus 9.1%), overall morbidity (18.0% versus 9.5%), surgical (12.7% versus 8.3%), and medical complications (9.0% versus 2.2%).ConclusionsThe NSQIP database allows for evaluation and comparison of reconstructive outcomes in the obese population. Increased BMI was associated with higher morbidity in autologous reconstruction than tissue expander reconstruction. Among autologous procedures, latissimus flaps experienced the lowest captured 30 day morbidity.