Pre-Emptive Acetaminophen for Postoperative Pain (PAPP): An Updated Meta-Analysis.

PURPOSE: Postoperative pain is a common consequence of surgery. Pre-emptive analgesia involves the initiation of analgesics prior to surgical incision. This has been proposed as a simple method to help reduce postoperative pain, which may be more effective in higher-risk populations such as cervical spine surgery. A previous meta-analysis has demonstrated that pre-emptive acetaminophen may be effective in reducing postoperative pain although the certainty of evidence was limited. This present paper is an updated meta-analysis comparing pre-emptive acetaminophen versus postincision acetaminophen in adult patients undergoing surgery. DESIGN: Systematic review and meta-analysis with the inclusion of an unpublished randomized, placebo-controlled, double-blind trial. METHODS: An updated meta-analysis was conducted which searched electronic databases to identify randomized controlled trials with the same interventions. FINDINGS: We included 845 participants and 12 studies in the updated meta-analysis. The meta-analysis (including our trial) found reduced 24-hour morphine consumption in the pre-emptive group (mean difference -2.42 mg; 95% confidence interval -4.26 to -0.59 mg), as well as reduced postoperative vomiting (risk ratio 0.56; 95% confidence interval 0.36 to 0.88). There was no difference between pre-emptive acetaminophen and control groups for time to analgesic request, pain scores at 6 and 24 hours or pruritis. For all outcomes assessed, there was very low certainty of evidence. CONCLUSIONS: This meta-analysis found pre-emptive acetaminophen reduced 24-hour opioid consumption and postoperative vomiting.

Appendectomy versus antibiotic treatment for acute appendicitis.

BACKGROUND: Acute appendicitis is one of the most common emergency general surgical conditions worldwide. Uncomplicated/simple appendicitis can be treated with appendectomy or antibiotics. Some studies have suggested possible benefits with antibiotics with reduced complications, length of hospital stay, and the number of days off work. However, surgery may improve success of treatment as antibiotic treatment is associated with recurrence and future need for surgery. OBJECTIVES: To assess the effects of antibiotic treatment for uncomplicated/simple acute appendicitis compared with appendectomy for resolution of symptoms and complications. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trial registers (World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov) on 19 July 2022. We also searched for unpublished studies in conference proceedings together with reference checking and citation search. There were no restrictions on date, publication status, or language of publication. SELECTION CRITERIA: We included parallel-group randomised controlled trials (RCTs) only. We included studies where most participants were adults with uncomplicated/simple appendicitis. Interventions included antibiotics (by any route) compared with appendectomy (open or laparoscopic). DATA COLLECTION AND ANALYSIS: We used standard methodology expected by Cochrane. We used GRADE to assess the certainty of evidence for each outcome. Primary outcomes included mortality and success of treatment, and secondary outcomes included number of participants requiring appendectomy in the antibiotic group, complications, pain, length of hospital stay, sick leave, malignancy in the antibiotic group, negative appendectomy rate, and quality of life. Success of treatment definitions were heterogeneous although mainly based on resolution of symptoms rather than incorporation of long-term recurrence or need for surgery in the antibiotic group. MAIN RESULTS: We included 13 studies in the review covering 1675 participants randomised to antibiotics and 1683 participants randomised to appendectomy. One study was unpublished. All were conducted in secondary care and two studies received pharmaceutical funding. All studies used broad-spectrum antibiotic regimens expected to cover gastrointestinal bacteria. Most studies used predominantly laparoscopic surgery, but some included mainly open procedures. Six studies included adults and children. Almost all studies aimed to exclude participants with complicated appendicitis prior to randomisation, although one study included 12% with perforation. The diagnostic technique was clinical assessment and imaging in most studies. Only one study limited inclusion by sex (male only). Follow-up ranged from hospital admission only to seven years. Certainty of evidence was mainly affected by risk of bias (due to lack of blinding and loss to follow-up) and imprecision. Primary outcomes It is uncertain whether there was any difference in mortality due to the very low-certainty evidence (Peto odds ratio (OR) 0.51, 95% confidence interval (CI) 0.05 to 4.95; 1 study, 492 participants). There may be 76 more people per 1000 having unsuccessful treatment in the antibiotic group compared with surgery, which did not reach our predefined level for clinical significance (risk ratio (RR) 0.91, 95% CI 0.87 to 0.96; I2 = 69%; 7 studies, 2471 participants; low-certainty evidence). Secondary outcomes At one year, 30.7% (95% CI 24.0 to 37.8; I2 = 80%; 9 studies, 1396 participants) of participants in the antibiotic group required appendectomy or, alternatively, more than two-thirds of antibiotic-treated participants avoided surgery in the first year, but the evidence is very uncertain. Regarding complications, it is uncertain whether there is any difference in episodes of Clostridium difficile diarrhoea due to very low-certainty evidence (Peto OR 0.97, 95% CI 0.24 to 3.89; 1 study, 1332 participants). There may be a clinically significant reduction in wound infections with antibiotics (RR 0.25, 95% CI 0.09 to 0.68; I2 = 16%; 9 studies, 2606 participants; low-certainty evidence). It is uncertain whether antibiotics affect the incidence of intra-abdominal abscess or collection (RR 1.58, 95% CI 0.61 to 4.07; I2 = 19%; 6 studies, 1831 participants), or reoperation (Peto OR 0.13, 95% CI 0.01 to 2.16; 1 study, 492 participants) due to very low-certainty evidence, mainly due to rare events causing imprecision and risk of bias. It is uncertain if antibiotics prolonged length of hospital stay by half a day due to the very low-certainty evidence (MD 0.54, 95% CI 0.06 to 1.01; I2 = 97%; 11 studies, 3192 participants). The incidence of malignancy was 0.3% (95% CI 0 to 1.5; 5 studies, 403 participants) in the antibiotic group although follow-up was variable. Antibiotics probably increased the number of negative appendectomies at surgery (RR 3.16, 95% CI 1.54 to 6.49; I2 = 17%; 5 studies, 707 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Antibiotics may be associated with higher rates of unsuccessful treatment for 76 per 1000 people, although differences may not be clinically significant. It is uncertain if antibiotics increase length of hospital stay by half a day. Antibiotics may reduce wound infections. A third of the participants initially treated with antibiotics required subsequent appendectomy or two-thirds avoided surgery within one year, but the evidence is very uncertain. There were too few data from the included studies to comment on major complications.

Non-opioid analgesics for the prevention of chronic postsurgical pain: a systematic review and network meta-analysis.

BACKGROUND: Chronic postsurgical pain is common after surgery. Identification of non-opioid analgesics with potential for preventing chronic postsurgical pain is important, although trials are often underpowered. Network meta-analysis offers an opportunity to improve power and to identify the most promising therapy for clinical use and future studies. METHODS: We conducted a PRISMA-NMA-compliant systematic review and network meta-analysis of randomised controlled trials of non-opioid analgesics for chronic postsurgical pain. Outcomes included incidence and severity of chronic postsurgical pain, serious adverse events, and chronic opioid use. RESULTS: We included 132 randomised controlled trials with 23 902 participants. In order of efficacy, i.v. lidocaine (odds ratio [OR] 0.32; 95% credible interval [CrI] 0.17-0.58), ketamine (OR 0.64; 95% CrI 0.44-0.92), gabapentinoids (OR 0.67; 95% CrI 0.47-0.92), and possibly dexmedetomidine (OR 0.36; 95% CrI 0.12-1.00) reduced the incidence of chronic postsurgical pain at ≤6 months. There was little available evidence for chronic postsurgical pain at >6 months, combinations agents, chronic opioid use, and serious adverse events. Variable baseline risk was identified as a potential violation to the network meta-analysis transitivity assumption, so results are reported from a fixed value of this, with analgesics more effective at higher baseline risk. The confidence in these findings was low because of problems with risk of bias and imprecision. CONCLUSIONS: Lidocaine (most effective), ketamine, and gabapentinoids could be effective in reducing chronic postsurgical pain ≤6 months although confidence is low. Moreover, variable baseline risk might violate transitivity in network meta-analysis of analgesics; this recommends use of our methods in future network meta-analyses. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42021269642.

Post-operative electrical muscle stimulation attenuates loss of muscle mass and function following major abdominal surgery in older adults: a split body randomised control trial.

INTRODUCTION: Significant losses of muscle mass and function occur after major abdominal surgery. Neuromuscular electrical stimulation (NMES) has been shown to reduce muscle atrophy in some patient groups, but evidence in post-operative patients is limited. This study assesses the efficacy of NMES for attenuating muscle atrophy and functional declines following major abdominal surgery in older adults. METHODS: Fifteen patients undergoing open colorectal resection completed a split body randomised control trial. Patients' lower limbs were randomised to control (CON) or NMES (STIM). The STIM limb underwent 15 minutes of quadriceps NMES twice daily on post-operative days (PODs) 1-4. Ultrasound measurements of Vastus Lateralis cross-sectional area (CSA) and muscle thickness (MT) were made preoperatively and on POD 5, as was dynamometry to determine knee extensor strength (KES). Change in CSA was the primary outcome. All outcomes were statistically analysed using linear mixed models. RESULTS: NMES significantly reduced the loss of CSA (-2.52 versus -9.16%, P < 0.001), MT (-2.76 versus -8.145, P = 0.001) and KES (-10.35 versus -19.69%, P = 0.03) compared to CON. No adverse events occurred, and patients reported that NMES caused minimal or no discomfort and felt that ~90-minutes of NMES daily would be tolerable. DISCUSSION: NMES reduces losses of muscle mass and function following major abdominal surgery, and as such, may be the promising tool for post-operative recovery. This is important in preventing long-term post-operative dependency, especially in the increasingly frail older patients undergoing major abdominal surgery. Further studies should establish the efficacy of bilateral NMES for improving patient-centred outcomes.

The time course of disuse muscle atrophy of the lower limb in health and disease.

Short, intermittent episodes of disuse muscle atrophy (DMA) may have negative impact on age related muscle loss. There is evidence of variability in rate of DMA between muscles and over the duration of immobilization. As yet, this is poorly characterized. This review aims to establish and compare the time-course of DMA in immobilized human lower limb muscles in both healthy and critically ill individuals, exploring evidence for an acute phase of DMA and differential rates of atrophy between and muscle groups. MEDLINE, Embase, CINHAL and CENTRAL databases were searched from inception to April 2021 for any study of human lower limb immobilization reporting muscle volume, cross-sectional area (CSA), architecture or lean leg mass over multiple post-immobilization timepoints. Risk of bias was assessed using ROBINS-I. Where possible meta-analysis was performed using a DerSimonian and Laird random effects model with effect sizes reported as mean differences (MD) with 95% confidence intervals (95% CI) at various time-points and a narrative review when meta-analysis was not possible. Twenty-nine studies were included, 12 in healthy volunteers (total n = 140), 18 in patients on an Intensive Therapy Unit (ITU) (total n = 516) and 3 in patients with ankle fracture (total n = 39). The majority of included studies are at moderate risk of bias. Rate of quadriceps atrophy over the first 14 days was significantly greater in the ITU patients (MD -1.01 95% CI -1.32, -0.69), than healthy cohorts (MD -0.12 95% CI -0.49, 0.24) (P < 0.001). Rates of atrophy appeared to vary between muscle groups (greatest in triceps surae (-11.2% day 28), followed by quadriceps (-9.2% day 28), then hamstrings (-6.5% day 28), then foot dorsiflexors (-3.2% day 28)). Rates of atrophy appear to decrease over time in healthy quadriceps (-6.5% day 14 vs. -9.1% day 28) and triceps surae (-7.8% day 14 vs. -11.2% day 28), and ITU quadriceps (-13.2% day 7 vs. -28.2% day 14). There appears to be variability in the rate of DMA between muscle groups, and more rapid atrophy during the earliest period of immobilization, indicating different mechanisms being dominant at different timepoints. Rates of atrophy are greater amongst critically unwell patients. Overall evidence is limited, and existing data has wide variability in the measures reported. Further work is required to fully characterize the time course of DMA in both health and disease.

The role of resistance exercise training for improving cardiorespiratory fitness in healthy older adults: a systematic review and meta-analysis.

BACKGROUND: Declines in cardiorespiratory fitness (CRF) and muscle mass are both associated with advancing age and each of these declines is associated with worse health outcomes. Resistance exercise training (RET) has previously been shown to improve muscle mass and function in the older population. If RET is also able to improve CRF, as it has been shown to do in younger populations, it has the potential to improve multiple health outcomes in the expanding older population. METHODS: This systematic review aimed to identify the role of RET for improving CRF in healthy older adults. A search across CINAHL, MEDLINE, EMBASE and EMCARE databases was conducted with meta-analysis performed on eligible papers to identify improvements in established CRF parameters (VO2 peak, aerobic threshold (AT), 6-minute walking distance test (6MWT) following RET intervention. Main eligibility criteria included older adults (aged over 60), healthy cohorts (disease-specific cohorts were excluded) and RET intervention. RESULTS: Thirty-seven eligible studies were identified. Meta-analysis revealed a significant improvement in VO2 peak (MD 1.89 ml/kg/min; 95% confidence interval (CI) 1.21-2.57 ml/kg/min), AT (MD 1.27 ml/kg/min; 95% CI 0.44-2.09 ml/kg/min) and 6MWT (MD 30.89; 95% CI 26.7-35.08) in RET interventions less than 24 weeks. There was no difference in VO2 peak or 6MWT in interventions longer than 24 weeks. DISCUSSION: This systematic review adds to a growing body of evidence supporting the implementation of RET in the older population for improving whole-body health, particularly in time-limited timeframes.

Dressings and topical agents for the management of open wounds after surgical treatment for sacrococcygeal pilonidal sinus.

BACKGROUND: Sacrococcygeal pilonidal sinus disease is a common debilitating condition that predominantly affects young adults, with a profound impact on their activities of daily living. The condition is treated surgically, and in some cases the wound in the natal cleft is left open to heal by itself. Many dressings and topical agents are available to aid healing of these wounds. OBJECTIVES: To assess the effects of dressings and topical agents for the management of open wounds following surgical treatment for sacrococcygeal pilonidal sinus in any care setting. SEARCH METHODS: In March 2021, we searched the Cochrane Wounds Specialised Register, CENTRAL, MEDLINE, Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and we scanned reference lists of included studies, reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We included parallel-group randomised controlled trials (RCTs) only. We included studies with participants who had undergone any type of sacrococcygeal pilonidal sinus disease surgery and were left with an open wound. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included 11 RCTs comprising 932 participants. Two studies compared topical negative pressure wound therapy (TNPWT) with conventional open wound healing, two studies compared platelet-rich plasma with sterile absorbent gauze, and the other seven studies compared various dressings and topical agents. All studies were at high risk of bias in at least one domain, whilst one study was judged to be at low risk of bias in all but one domain. All studies were conducted in secondary care. Mean participant ages were between 20 and 30 years, and nearly 80% of participants were male. No studies provided data on quality of life, cost-effectiveness, pain at first dressing change or proportion of wounds healed at 6 or 12 months, and very few adverse effects were recorded in any study. It is unclear whether TNPWT reduces time to wound healing compared with conventional open wound healing (comparison 1), as the certainty of evidence is very low. The two studies provided conflicting results, with one study showing benefit (mean difference (MD) -24.01 days, 95% confidence interval (CI) -35.65 to -12.37; 19 participants), whilst the other reported no difference. It is also unclear whether TNPWT has any effect on the proportion of wounds healed by 30 days (risk ratio (RR) 3.60, 95% CI 0.49 to 26.54; 19 participants, 1 study; very low-certainty evidence). Limited data were available for our secondary outcomes time to return to normal daily activities and recurrence rate; we do not know whether TNPWT has any effect on these outcomes. Lietofix cream may increase the proportion of wounds that heal by 30 days compared with an iodine dressing (comparison 4; RR 8.06, 95% CI 1.05 to 61.68; 205 participants, 1 study; low-certainty evidence). The study did not provide data on time to wound healing. We do not know whether hydrogel dressings reduce time to wound healing compared with wound cleaning with 10% povidone iodine (comparison 5; MD -24.54 days, 95% CI -47.72 to -1.36; 31 participants, 1 study; very low-certainty evidence). The study did not provide data on the proportion of wounds healed. It is unclear whether hydrogel dressings have any effect on adverse effects as the certainty of the evidence is very low. Platelet-rich plasma may reduce time to wound healing compared with sterile absorbent gauze (comparison 6; MD -19.63 days, 95% CI -34.69 to -4.57; 210 participants, 2 studies; low-certainty evidence). No studies provided data on the proportion of wounds healed. Platelet-rich plasma may reduce time to return to normal daily activities (MD -15.49, 95% CI -28.95 to -2.02; 210 participants, 2 studies; low-certainty evidence). Zinc oxide mesh may make little or no difference to time to wound healing compared with placebo (comparison 2; median 54 days in the zinc oxide mesh group versus 62 days in the placebo mesh group; low-certainty evidence). We do not know whether zinc oxide mesh has an effect on the proportion of wounds healed by 30 days as the certainty of the evidence is very low (RR 2.35, 95% CI 0.49 to 11.23). It is unclear whether gentamicin-impregnated collagen sponge reduces time to wound healing compared with no dressing (comparison 7; MD -1.40 days, 95% CI -5.05 to 2.25; 50 participants, 1 study; very low-certainty evidence). The study did not provide data on the proportion of wounds healed. Dialkylcarbamoyl chloride (DACC)-coated dressings may make little or no difference to time to wound healing compared with alginate dressings (comparison 8; median 69 (95% CI 62 to 72) days in the DACC group versus 71 (95% CI 69 to 85) days in the alginate group; 1 study, 246 participants; low-certainty evidence). One study compared a polyurethane foam hydrophilic dressing with an alginate dressing (comparison 3) whilst another study compared a hydrocolloid dressing with an iodine dressing (comparison 9). It is unclear whether either intervention has any effect on time to wound healing as the certainty of evidence is very low. AUTHORS' CONCLUSIONS: At present, the evidence that any of the dressings or topical agents contained in this review have a benefit on time to wound healing, the proportion of wounds that heal at a specific time point or on any of the secondary outcomes of our review ranges from low certainty to very low certainty. There is low-certainty evidence on the benefit on wound healing of platelet-rich plasma from two studies and of Lietofix cream and hydrogel dressings from single studies. Further studies are required to investigate these interventions further.

The physiological impact of high-intensity interval training in octogenarians with comorbidities.

BACKGROUND: Declines in cardiorespiratory fitness (CRF) and fat-free mass (FFM) with age are linked to mortality, morbidity and poor quality of life. High-intensity interval training (HIIT) has been shown to improve CRF and FFM in many groups, but its efficacy in the very old, in whom comorbidities are present is undefined. We aimed to assess the efficacy of and physiological/metabolic responses to HIIT, in a cohort of octogenarians with comorbidities (e.g. hypertension and osteoarthritis). METHODS: Twenty-eight volunteers (18 men, 10 women, 81.2 ± 0.6 years, 27.1 ± 0.6 kg·m-2 ) with American Society of Anaesthesiology (ASA) Grade 2-3 status each completed 4 weeks (12 sessions) HIIT after a control period of equal duration. Before and after each 4 week period, subjects underwent body composition assessments and cardiopulmonary exercise testing. Quadriceps muscle biopsies (m. vastus lateralis) were taken to quantify anabolic signalling, mitochondrial oxidative phosphorylation, and cumulative muscle protein synthesis (MPS) over 4-weeks. RESULTS: In comorbid octogenarians, HIIT elicited improvements in CRF (anaerobic threshold: +1.2 ± 0.4 ml·kg-1 ·min-1 , P = 0.001). HIIT also augmented total FFM (47.2 ± 1.4 to 47.6 ± 1.3 kg, P = 0.04), while decreasing total fat mass (24.8 ± 1.3 to 24 ± 1.2 kg, P = 0.0002) and body fat percentage (33.1 ± 1.5 to 32.1 ± 1.4%, P = 0.0008). Mechanistically, mitochondrial oxidative phosphorylation capacity increased after HIIT (i.e. citrate synthase activity: 52.4 ± 4 to 67.9 ± 5.1 nmol·min-1 ·mg-1 , P = 0.005; membrane protein complexes (C): C-II, 1.4-fold increase, P = 0.002; C-III, 1.2-fold increase, P = 0.03), as did rates of MPS (1.3 ± 0.1 to 1.5 ± 0.1%·day-1 , P = 0.03). The increase in MPS was supported by up-regulated phosphorylation of anabolic signalling proteins (e.g. AKT, p70S6K, and 4E-BP1; all P < 0.05). There were no changes in any of these parameters during the control period. No adverse events were reported throughout the study. CONCLUSIONS: The HIIT enhances skeletal muscle mass and CRF in octogenarians with disease, with up-regulation of MPS and mitochondrial capacity likely underlying these improvements. HIIT can be safely delivered to octogenarians with disease and is an effective, time-efficient intervention to improve muscle mass and physical function in a short time frame.

Pre-emptive and preventive NSAIDs for postoperative pain in adults undergoing all types of surgery.

BACKGROUND: Postoperative pain is a common consequence of surgery and can have many negative perioperative effects. It has been suggested that the administration of analgesia before a painful stimulus may improve pain control. We defined pre-emptive nonsteroidal anti-inflammatories (NSAIDs) as those given before surgery but not continued afterwards and preventive NSAIDs as those given before surgery and continued afterwards. These were compared to a control group given the NSAIDs after surgery instead of before surgery. OBJECTIVES: To assess the efficacy of preventive and pre-emptive NSAIDs for reducing postoperative pain in adults undergoing all types of surgery. SEARCH METHODS: We searched the following electronic databases: CENTRAL, MEDLINE, Embase, AMED and CINAHL (up to June 2020). In addition, we searched for unpublished studies in three clinical trial databases, conference proceedings, grey literature databases, and reference lists of retrieved articles. We did not apply any restrictions on language or date of publication. SELECTION CRITERIA: We included parallel-group randomized controlled trials (RCTs) only. We included adult participants undergoing any type of surgery. We defined pre-emptive NSAIDs as those given before surgery but not continued afterwards and preventive NSAIDs as those given before surgery and continued afterwards. These were compared to a control group given the NSAIDs after surgery instead of before surgery. We included studies that gave the medication by any route but not given on the skin. DATA COLLECTION AND ANALYSIS: We used the standard methods expected by Cochrane, as well as a novel publication bias test developed by our research group. We used GRADE to assess the certainty of the evidence for each outcome. Outcomes included acute postoperative pain (minimal clinically important difference (MCID): 1.5 on a 0-10 scale), adverse events of NSAIDs, nausea and vomiting, 24-hour morphine consumption (MCID: 10 mg reduction), time to analgesic request (MCID: one hour), pruritus, sedation, patient satisfaction, chronic pain and time to first bowel movement (MCID: 12 hours). MAIN RESULTS: We included 71 RCTs. Seven studies are awaiting classification. We included 45 studies that evaluated pre-emptive NSAIDs and 26 studies that evaluated preventive NSAIDs. We considered only four studies to be at low risk of bias for most domains. The operations and NSAIDs used varied, although most studies were conducted in abdominal, orthopaedic and dental surgery. Most studies were conducted in secondary care and in low-risk participants. Common exclusions were participants on analgesic medications prior to surgery and those with chronic pain. Pre-emptive NSAIDs compared to post-incision NSAIDs For pre-emptive NSAIDs, there is probably a decrease in early acute postoperative pain (MD -0.69, 95% CI -0.97 to -0.41; studies = 36; participants = 2032; I2 = 96%; moderate-certainty evidence). None of the included studies that reported on acute postoperative pain reported adverse events as an outcome. There may be little or no difference between the groups in short-term (RR 1.00, 95% CI 0.34 to 2.94; studies = 2; participants = 100; I2 = 0%; low-certainty evidence) or long-term nausea and vomiting (RR 0.85, 95% CI 0.52 to 1.38; studies = 5; participants = 228; I2 = 29%; low-certainty evidence). There may be a reduction in late acute postoperative pain (MD -0.22, 95% CI -0.44 to 0.00; studies = 28; participants = 1645; I2 = 97%; low-certainty evidence). There may be a reduction in 24-hour morphine consumption with pre-emptive NSAIDs (MD -5.62 mg, 95% CI -9.00 mg to -2.24 mg; studies = 16; participants = 854; I2 = 99%; low-certainty evidence) and an increase in the time to analgesic request (MD 17.04 minutes, 95% CI 3.77 minutes to 30.31 minutes; studies = 18; participants = 975; I2 = 95%; low-certainty evidence). There may be little or no difference in opioid adverse events such as pruritus (RR 0.40, 95% CI 0.09 to 1.76; studies = 4; participants = 254; I2 = 0%; low-certainty evidence) or sedation (RR 0.51, 95% CI 0.16 to 1.68; studies = 4; participants = 281; I2 = 0%; low-certainty evidence), although the number of included studies for these outcomes was small. No study reported patient satisfaction, chronic pain or time to first bowel movement for pre-emptive NSAIDs. Preventive NSAIDs compared to post-incision NSAIDs For preventive NSAIDs, there may be little or no difference in early acute postoperative pain (MD -0.14, 95% CI -0.39 to 0.12; studies = 18; participants = 1140; I2 = 75%; low-certainty evidence). One study reported adverse events from NSAIDs (reoperation for bleeding) although the events were low which did not allow any meaningful conclusions to be drawn (RR 1.95; 95% CI 0.18 to 20.68). There may be little or no difference in rates of short-term (RR 1.26, 95% CI 0.49 to 3.30; studies = 1; participants = 76; low-certainty evidence) or long-term (RR 0.85, 95% CI 0.52 to 1.38; studies = 5; participants = 456; I2 = 29%; low-certainty evidence) nausea and vomiting. There may be a reduction in late acute postoperative pain (MD -0.33, 95% CI -0.59 to -0.07; studies = 21; participants = 1441; I2 = 81%; low-certainty evidence). There is probably a reduction in 24-hour morphine consumption (MD -1.93 mg, 95% CI -3.55 mg to -0.32 mg; studies = 16; participants = 1323; I2 = 49%; moderate-certainty evidence). It is uncertain if there is any difference in time to analgesic request (MD 8.51 minutes, 95% CI -31.24 minutes to 48.27 minutes; studies = 8; participants = 410; I2 = 98%; very low-certainty evidence). As with pre-emptive NSAIDs, there may be little or no difference in other opioid adverse events such as pruritus (RR 0.56, 95% CI 0.09 to 3.35; studies = 3; participants = 211; I2 = 0%; low-certainty evidence) and sedation (RR 0.84, 95% CI 0.44 to 1.63; studies = 5; participants = 497; I2 = 0%; low-certainty evidence). There is probably little or no difference in patient satisfaction (MD -0.42; 95% CI -1.09 to 0.25; studies = 1; participants = 72; moderate-certainty evidence). No study reported on chronic pain. There is probably little or no difference in time to first bowel movement (MD 0.00; 95% CI -15.99 to 15.99; studies = 1; participants = 76; moderate-certainty evidence). AUTHORS' CONCLUSIONS: There was some evidence that pre-emptive and preventive NSAIDs reduce both pain and morphine consumption, although this was not universal for all pain and morphine consumption outcomes. Any differences found were not clinically significant, although we cannot exclude this in more painful operations. Moreover, without any evidence of reductions in opioid adverse effects, the clinical significance of these results is questionable although few studies reported these outcomes. Only one study reported clinically significant adverse events from NSAIDs administered before surgery and, therefore, we have very few data to assess the safety of either pre-emptive or preventive NSAIDs. Therefore, future research should aim to adhere to the highest methodology and be adequately powered to assess serious adverse events of NSAIDs and reductions in opioid adverse events.

Contrast-enhanced ultrasound assessed renal microvascular perfusion may predict postoperative renal complications following colorectal surgery.

Colorectal surgery is associated with an above-average mortality rate of approximately 15%. During surgery, maintenance of vital organ perfusion is essential in order to reduce postoperative mortality and morbidity, with renal perfusion of particular importance. Oesophageal Doppler monitors (ODM) are commonly used to try and provide accurate measures of fluid depletion during surgery; however, it is unclear to what extent they reflect organ perfusion. In addition, it is not known whether macro- and/ or microvascular perfusion indices are associated with renal complications following colorectal surgery. Thirty-two participants scheduled for colorectal surgery had three measures of macro- and microvascular renal blood flow via contrast enhanced ultrasound (CEUS), and simultaneous measures of cardiac output indices via ODM: (i) pre-operatively; (ii) intra-operatively at the mid-point of operation, and (iii) after the conclusion of surgery. The Postoperative Morbidity Survey (POMS) was used to assess postoperative complications. Intra-operatively, there was a significant correlation between renal microvascular flow (RT) and renal macrovascular flow (TTI) (ρ = 0.52; p = 0.003). Intra-operative TTI, but not RT, was associated with cardiac index (ρ = -0.50; p=0.0003). Intra-operative RT predicted increases in renal complications (OR 1.46; 95% CI 1.03-2.09) with good discrimination (C-statistic, 0.85). Complications were not predicted by TTI or ODM-derived indices. There was no relationship between RT and TTI before or after surgery. ODM measures of haemodynamic status do not correlate with renal microvascular blood flow, and as such are likely not suitable to determine vital organ perfusion. Only CEUS-derived measures of microvascular perfusion were predictive of postoperative renal complications.

A double-blind randomized controlled trial of the effects of eicosapentaenoic acid supplementation on muscle inflammation and physical function in patients undergoing colorectal cancer resection.

BACKGROUND: Resection of colorectal cancer (CRC) initiates inflammation, mediated at least partly by NFĸB (nuclear factor kappa-light-chain-enhancer of activated B-cells), leading to muscle catabolism and reduced physical performance. Eicosapentaenoic acid (EPA) has been shown to modulate NFĸB, but evidence for its benefit around the time of surgery is limited. OBJECTIVE: To assess the effect of EPA supplementation on muscle inflammation and physical function around the time of major surgery. DESIGN: In a double-blind randomized control trial, 61 patients (age: 68.3 ± 0.95 y; 42 male) scheduled for CRC resection, received 3 g per day of EPA (n = 32) or placebo (n = 29) for 5-days before and 21-days after operation. Lean muscle mass (LMM) (via dual energy X-ray absorptiometry (DXA)), anaerobic threshold (AT) (via cardiopulmonary exercise testing (CPET)) and hand-grip strength (HG) were assessed before and 4-weeks after surgery, with muscle biopsies (m. vastus lateralis) obtained for the assessment of NF-ĸB protein expression. RESULTS: There were no differences in muscle NFĸB between EPA and placebo groups (mean difference (MD) -0.002; 95% confidence interval (CI) -0.19 to 0.19); p = 0.98). There was no difference in LMM (MD 704.77 g; 95% CI -1045.6 g-2455.13 g; p = 0.42) or AT (MD 1.11 mls/kg/min; 95% CI -0.52 mls/kg/min to 2.74 mls/kg/min; p = 0.18) between the groups. Similarly, there was no difference between the groups in HG at follow up (MD 0.1; 95% CI -1.88 to 2.08; p = 0.81). Results were similar when missing data was imputed. CONCLUSION: EPA supplementation confers no benefit in terms of inflammatory status, as judged by NFĸB, or preservation of LMM, aerobic capacity or physical function following major colorectal surgery. CLINICAL TRIALS REFERENCE: NCT01320319.

Surgical interventions for the treatment of sacrococcygeal pilonidal sinus disease in children: A systematic review and meta-analysis.

BACKGROUND: Pilonidal sinus disease (PNS) is not uncommon in children. Controversy remains over the best treatment and there is limited evidence. This systematic review and meta-analysis aims to establish which techniques have the best outcomes in children. METHODS: MEDLINE, EMBASE and CENTRAL databases were searched. Studies reporting treatment outcomes for PNS in children were included. RESULTS: Open healing has pooled risk of recurrence of 26% (95%CI 15-38%), risk of wound complication of 21% (9-36%) and wound healing ranged from 38-92 days. Midline primary closure has pooled risk of recurrence of 12% (8-18%), risk of wound complication of 30% (19-46%) and wound healing ranged from 8 to 32 days. Off-midline primary closure has pooled risk of recurrence of 6% (1-15%), risk of wound complication of 14% (6-25%) and wound healing was 27 days. VAC therapy has pooled risk of recurrence of 20% (0-65%) and wound healing ranged from 38 to 92 days. Minimally invasive techniques has pooled risk of recurrence of 7% (1-16%) and wound healing ranged from 21-30 days. Marsupialisation has pooled risk of recurrence of 6% (0-22%), and wound healing ranged from 6 to 41 days. CONCLUSION: Evidence for management of PNS in children is poor. Off-midline primary closure, minimally invasive techniques, and marsupialisation have the best outcomes. LEVEL OF EVIDENCE RATING: IV.

Pre-emptive and preventive opioids for postoperative pain in adults undergoing all types of surgery.

BACKGROUND: Postoperative pain is a common consequence of surgery and can have deleterious effects. It has been suggested that the administration of opioid analgesia before a painful stimulus may improve pain control. This can be done in two ways. We defined 'preventive opioids' as opioids administered before incision and continued postoperatively, and 'pre-emptive opioids' as opioids given before incision but not continued postoperatively. Both pre-emptive and preventive analgesia involve the initiation of an analgesic agent prior to surgical incision with the aim of reducing intraoperative nociception and therefore postoperative pain. OBJECTIVES: To assess the efficacy of preventive and pre-emptive opioids for reducing postoperative pain in adults undergoing all types of surgery. SEARCH METHODS: We searched the following electronic databases: CENTRAL, MEDLINE, Embase, AMED, and CINAHL (up to 18 March 2018). In addition, we searched for unpublished studies in three clinical trial databases, conference proceedings, grey literature databases, and reference lists of retrieved articles. We did not apply any restrictions on language or date of publication. SELECTION CRITERIA: We included parallel-group randomized controlled trials (RCTs) only. We included participants aged over 15 years old undergoing any type of surgery. We defined postincision opioids as the same intervention administered after incision whether single dose (as comparator with pre-emptive analgesia) or continued postoperatively (as comparator with preventive analgesia) (control group). We considered studies that did and did not use a double-dummy placebo (e.g. intervention group received active drug before incision and placebo after incision; control group received placebo before incision and active drug after incision). DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were: early acute postoperative pain (measured within six hours and reported on a 0-to-10 scale) and respiratory depression. Our secondary outcomes included: late acute postoperative pain (24 to 48 hours and reported on a 0-to-10 scale), 24-hour morphine consumption, and adverse events (intraoperative bradycardia and hypotension). We used GRADE to assess the quality of the evidence for each outcome. MAIN RESULTS: We included 20 RCTs, including one unpublished study with 1343 participants. Two studies were awaiting classification as the full text for these studies was not available. One study evaluated pre-emptive opioids, and 19 studies evaluated preventive opioids. We considered only one study to be at low risk of bias for most domains. The surgeries and opioids used varied, although roughly half of the included studies were conducted in abdominal hysterectomy, and around a quarter used morphine as the intervention. All studies were conducted in secondary care.Pre-emptive opioids compared to postincision opioidsFor pre-emptive opioids in dental surgery, there may be a reduction in early acute postoperative pain (mean difference (MD) -1.20, 95% confidence interval (CI) -1.75 to -0.65; 40 participants; 1 study; low-quality evidence). This study did not report on adverse events (respiratory depression, bradycardia, or hypotension). There may be a reduction in late acute postoperative pain (MD -2.10, 95% CI -2.57 to -1.63; 40 participants; 1 study; low-quality evidence). This study did not report 24-hour morphine consumption.Preventive opioids compared to postincision opioidsFor preventive opioids, there was probably no reduction in early acute postoperative pain (MD 0.11, 95% CI -0.32 to 0.53; 706 participants; 10 studies; I2 = 61%; moderate-quality evidence). There were no events of respiratory depression in four studies (433 participants). There was no important reduction in late acute postoperative pain (MD -0.06, 95% CI -0.13 to 0.01; 668 participants; 9 studies; I2 = 0%; moderate-quality evidence). There may be a small reduction in 24-hour morphine consumption (MD -4.91 mg, 95% CI -9.39 mg to -0.44 mg; 526 participants; 11 studies; I2 = 82%; very low-quality evidence). There may be similar rates of bradycardia (risk ratio (RR) 0.33, 95% CI 0.01 to 7.88; 112 participants; 2 studies; I2 = 0%; low-quality evidence) and hypotension (RR 1.08, 95% CI 0.25 to 4.73; 88 participants; 2 studies; I2 = 0%; low-quality evidence). AUTHORS' CONCLUSIONS: Due to the low quality of the evidence, we are uncertain whether pre-emptive opioids reduce postoperative pain. Based on the trials conducted thus far, there was no clear evidence that preventive opioids result in reductions in pain scores. It was unclear if there was a reduction in morphine consumption due to very low-quality of evidence. Too few studies reported adverse events to be able to draw any definitive conclusions. Once assessed, the two studies awaiting classification may alter the conclusions of the review.

The Use of Cannabinoids in Colitis: A Systematic Review and Meta-Analysis.

Background: Clinical trials investigating the use of cannabinoid drugs for the treatment of intestinal inflammation are anticipated secondary to preclinical literature demonstrating efficacy in reducing inflammation. Methods: We systematically reviewed publications on the benefit of drugs targeting the endo-cannabinoid system in intestinal inflammation. We collated studies examining outcomes for meta-analysis from EMBASE, MEDLINE and Pubmed until March 2017. Quality was assessed according to mSTAIR and SRYCLE score. Results: From 2008 papers, 51 publications examining the effect of cannabinoid compounds on murine colitis and 2 clinical studies were identified. Twenty-four compounds were assessed across 71 endpoints. Cannabidiol, a phytocannabinoid, was the most investigated drug. Macroscopic colitis severity (disease activity index [DAI]) and myeloperoxidase activity (MPO) were assessed throughout publications and were meta-analyzed using random effects models. Cannabinoids reduced DAI in comparison with the vehicle (standard mean difference [SMD] -1.36; 95% CI, -1.62 to-1.09; I2 = 61%). FAAH inhibitor URB597 had the largest effect size (SMD -4.43; 95% CI, -6.32 to -2.55), followed by the synthetic drug AM1241 (SMD -3.11; 95% CI, -5.01 to -1.22) and the endocannabinoid anandamide (SMD -3.03; 95% CI, -4.89 to -1.17; I2 not assessed). Cannabinoids reduced MPO in rodents compared to the vehicle; SMD -1.26; 95% CI, -1.54 to -0.97; I2 = 48.1%. Cannabigerol had the largest effect size (SMD -6.20; 95% CI, -9.90 to -2.50), followed by the synthetic CB1 agonist ACEA (SMD -3.15; 95% CI, -4.75 to -1.55) and synthetic CB1/2 agonist WIN55,212-2 (SMD -1.74; 95% CI, -2.81 to -0.67; I2 = 57%). We found no evidence of reporting bias. No significant difference was found between the prophylactic and therapeutic use of cannabinoid drugs. Conclusions: There is abundant preclinical literature demonstrating the anti-inflammatory effects of cannabinoid drugs in inflammation of the gut. Larger randomised controlled-trials are warranted.

Baseline Morphine Consumption May Explain Between-Study Heterogeneity in Meta-analyses of Adjuvant Analgesics and Improve Precision and Accuracy of Effect Estimates.

BACKGROUND: Statistical heterogeneity can increase the uncertainty of results and reduce the quality of evidence derived from systematic reviews. At present, it is uncertain what the major factors are that account for heterogeneity in meta-analyses of analgesic adjuncts. Therefore, the aim of this review was to identify whether various covariates could explain statistical heterogeneity and use this to improve accuracy when reporting the efficacy of analgesics. METHODS: We searched for reviews using MEDLINE, EMBASE, CINAHL, AMED, and the Cochrane Database of Systematic Reviews. First, we identified the existence of considerable statistical heterogeneity (I > 75%). Second, we conducted meta-regression analysis for the outcome of 24-hour morphine consumption using baseline risk (control group morphine consumption) and other clinical and methodological covariates. Finally, we constructed a league table of adjuvant analgesics using a novel method of reporting effect estimates assuming a fixed consumption of 50 mg postoperative morphine. RESULTS: We included 344 randomized controlled trials with 28,130 participants. Ninety-one percent of analyses showed considerable statistical heterogeneity. Baseline risk was a significant cause of between-study heterogeneity for acetaminophen, nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors, tramadol, ketamine, α2-agonists, gabapentin, pregabalin, lidocaine, magnesium, and dexamethasone (R = 21%-100%; P < .05). There was some evidence that the methodological limitations of the trials explained some of the residual heterogeneity. Type of surgery was not independently associated with analgesic efficacy. Assuming a fixed baseline risk of 50 mg (in order of efficacy), gabapentin, acetaminophen, α2-agonists, nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors, pregabalin, tramadol, magnesium, and lidocaine demonstrated moderate clinically significant reductions (>10 mg). We could not exclude a moderate clinically significant effect with ketamine. Dexamethasone demonstrated a small clinical benefit (>5 mg). CONCLUSIONS: We empirically identified baseline morphine consumption as the major source of heterogeneity in meta-analyses of adjuvant analgesics across all surgical interventions. Controlling for baseline morphine consumption, clinicians can use audit data to estimate the morphine-reducing effect of adding any adjuvant for their local population, regardless which surgery they undergo. Moreover, we have utilized these findings to present a novel method of reporting and an amended method of graphically displaying effect estimates, which both reduces confounding from variable baseline risk in included trials and is able to adjust for other clinical and methodological confounding variables. We recommend use of these methods in clinical practice and future reviews of analgesics for postoperative pain.

Fibrin glue for pilonidal sinus disease.

BACKGROUND: Pilonidal sinus disease is a common condition that mainly affects young adults. This condition can cause significant pain and impairment of normal activities. No consensus currently exists on the optimum treatment for pilonidal sinus and current therapies have various advantages and disadvantages. Fibrin glue has emerged as a potential treatment as both monotherapy and an adjunct to surgery. OBJECTIVES: To assess the effects of fibrin glue alone or in combination with surgery compared with surgery alone in the treatment of pilonidal sinus disease. SEARCH METHODS: In December 2016 we searched: the Cochrane Wounds Specialised Register; CENTRAL; MEDLINE; Embase and CINAHL Plus. We also searched clinical trials registries and conference proceedings for ongoing and unpublished studies and scanned reference lists to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We included randomised controlled trials (RCTs) only. We included studies involving participants of all ages and studies conducted in any setting. We considered studies involving people with both new and recurrent pilonidal sinus. We included studies which evaluated fibrin glue monotherapy or as an adjunct to surgery. DATA COLLECTION AND ANALYSIS: Two study authors independently extracted data and assessed risk of bias. We used standard methods expected by Cochrane. MAIN RESULTS: We included four RCTs with 253 participants, all were at risk of bias. One unpublished study evaluated fibrin glue monotherapy compared with Bascom's procedure, two studies evaluated fibrin glue as an adjunct to Limberg flap and one study evaluated fibrin glue as an adjunct to Karydakis flap.For fibrin glue monotherapy compared with Bascom's procedure, there were no data available for the primary outcomes of time to healing and adverse events. There was low-quality evidence of less pain on day one after the procedure with fibrin glue monotherapy compared with Bascom's procedure (mean difference (MD) -2.50, 95% confidence interval (CI) -4.03 to -0.97) (evidence downgraded twice for risk of performance and detection bias). Fibrin glue may reduce the time taken to return to normal activities compared with Bascom's procedure (mean time 42 days with surgery and 7 days with glue, MD -34.80 days, 95% CI -66.82 days to -2.78 days) (very low-quality evidence, downgraded as above and for imprecision).Fibrin glue as an adjunct to the Limberg flap may reduce the healing time from 22 to 8 days compared with the Limberg flap alone (MD -13.95 days, 95% CI -16.76 days to -11.14 days) (very low-quality evidence, downgraded twice for risk of selection, performance and detection bias and imprecision). It is uncertain whether use of fibrin glue affects the incidence of postoperative seroma (an adverse event) (risk ratio (RR) 0.27, 95% CI 0.05 to 1.61; very low-quality evidence, downgraded twice for risk of selection, performance and detection bias and imprecision). There was low-quality evidence that fibrin glue, as an adjunct to Limberg flap, may reduce postoperative pain (median 2 versus 4; P < 0.001) and time to return to normal activities (median 8 days versus 17 days; P < 0.001). The addition of fibrin glue to the Limberg flap may reduce the length of hospital stay (MD -1.69 days, 95% CI -2.08 days to -1.29 days) (very low-quality evidence, downgraded twice for risk of selection, performance and detection bias and for unexplained heterogeneity).A single RCT evaluating fibrin glue as an adjunct to the Karydakis flap did not report data for the primary outcome of time to healing. It is uncertain whether fibrin glue with the Karydakis flap affects the incidence of postoperative seroma (adverse event) (RR 3.00, 95% CI 0.67 to 13.46) (very low-quality evidence, downgraded twice for risk of selection, performance and detection bias and for imprecision). Fibrin glue as an adjunct to Karydakis flap may reduce length of stay but this is highly uncertain (mean 2 days versus 3.7 days; P < 0.001, low-quality evidence downgraded twice for risk of selection, performance and detection bias). AUTHORS' CONCLUSIONS: Current evidence is uncertain regarding any benefits associated with fibrin glue either as monotherapy or as an adjunct to surgery for people with pilonidal sinus disease. We identified only four RCTs and each was small and at risk of bias resulting in very low-quality evidence for the primary outcomes of time to healing and adverse events. Future studies should enrol many more participants, ensure adequate randomisation and blinding, whilst measuring clinically relevant outcomes.

Gabapentin for the hemodynamic response to intubation: systematic review and meta-analysis.

PURPOSE: Endotracheal intubation is the gold standard for securing the airway before surgery. Nevertheless, this procedure can produce an activation of the sympathetic nervous system and result in a hemodynamic response which, in high-risk patients, may lead to cardiovascular instability and myocardial ischemia. The aim of this review was to evaluate whether gabapentin can attenuate this response and whether such an attenuation could translate into reduced myocardial ischemia and mortality. SOURCE: We searched MEDLINE(®), EMBASE™, CINAHL, AMED, and unpublished clinical trial databases for randomized-controlled trials that compared gabapentin with control, fentanyl, clonidine, or beta blockers for attenuating the hemodynamic response to intubation. Primary outcomes were mortality, myocardial infarction, and myocardial ischemia. Secondary outcomes were hemodynamic changes following intubation. PRINCIPAL FINDINGS: We included 29 randomized trials with only two studies at low risk of bias. No data were provided for the primary outcomes and no studies included high-risk patients. The use of gabapentin resulted in attenuation in the rise in mean arterial blood pressure [mean difference (MD), -12 mmHg; 95% confidence interval (CI), -17 to -8] and heart rate (MD, -8 beats·min(-1); 95% CI, -11 to -5) one minute after intubation. Gabapentin also reduced the risk of hypertension or tachycardia requiring treatment (risk ratio, 0.15; 95% CI, 0.05 to 0.48). Data were limited on adverse hemodynamic events such as bradycardia and hypotension. CONCLUSION: It remains unknown whether gabapentin improves clinically relevant outcomes such as death and myocardial infarction since studies failed to report on these. Nevertheless, gabapentin attenuated increases in heart rate and blood pressure following intubation when compared with the control group. Even so, the studies included in this review were at potential risk of bias. Moreover, they did not include high-risk patients or report adverse hemodynamic outcomes. Future studies are required to address these limitations.

Preventive Acetaminophen Reduces Postoperative Opioid Consumption, Vomiting, and Pain Scores After Surgery: Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Preventive analgesia has been proposed as a potential strategy to reduce postoperative pain. However, there is currently no review that focuses on acetaminophen for preventive analgesia. METHODS: We conducted a search of MEDLINE, EMBASE, Cinahl, AMED, and CENTRAL databases identifying randomized controlled trials that compared preventive acetaminophen with postincision acetaminophen. RESULTS: Seven studies with 544 participants were included. Overall, the studies showed a reduction in 24-hour opioid consumption (standardized mean difference [SMD] of -0.52; 95% confidence interval [95% CI], -0.98 to -0.06), lower pain scores at 1 hour (MD, -0.50; 95% CI, -0.98 to -0.02) and 2 hours (MD, -0.34; 95% CI, -0.67 to -0.01), and a lower incidence of postoperative vomiting (risk ratio, 0.50; 95% CI, 0.31-0.83) in the preventive acetaminophen group. Current studies are limited by a potential risk of bias. CONCLUSIONS: To our knowledge, this is the first review to describe a potential preventive effect of acetaminophen. However, well-conducted randomized controlled trials are necessary to substantiate the conclusions of this review.

Rupture of the Left External Iliac Artery and Right Groin Pseudoaneurysm Formation following Angioplasty in a Patient with Neurofibromatosis Type 1 and Undiagnosed Bilateral Phaeochromocytoma.

Neurofibromatosis type 1 (NF1) is a genetic condition, which affects 1 in every 3000 births. Patients with NF1 are at increased risk of a variety of vascular abnormalities. This report presents the case of a 60-year-old male with NF1 who suffered a left external iliac rupture and a right pseudoaneurysm following angioplasty. In addition, these were further complicated by previously undiagnosed, bilateral phaeochromocytomas. The inherent weakness in vessel wall architecture found in NF1 coupled with the hypertension evident during and after the procedure contributed to haemorrhage and pseudoaneurysm formation. Caution must be taken in such patients when considering vascular intervention.