Gerard F. Curley

The Analgesic Efficacy of Transversus Abdominis Plane Block After Abdominal Surgery: A Prospective Randomized Controlled Trial

BACKGROUND:The transversus abdominis plane (TAP) block is a novel approach for blocking the abdominal wall neural afferents via the bilateral lumbar triangles of Petit. We evaluated its analgesic efficacy in patients during the first 24 postoperative hours after abdominal surgery, in a randomized, controlled, double-blind clinical trial. METHODS:Thirty-two adults undergoing large bowel resection via a midline abdominal incision were randomized to receive standard care, including patient-controlled morphine analgesia and regular nonsteroidal antiinflammatory drugs and acetaminophen (n = 16), or to undergo TAP block (n = 16) in addition to standard care (n = 16). After induction of anesthesia, 20 mL of 0.375% levobupivacaine was deposited into the transversus abdominis neuro-fascial plane via the bilateral lumbar triangles of Petit. Each patient was assessed by a blinded investigator in the postanesthesia care unit and at 2, 4, 6, and 24 h postoperatively. RESULTS:The TAP block reduced visual analog scale pain scores (TAP versus control, mean ± sd) on emergence (1 ± 1.4 vs 6.6 ± 2.8, P < 0.05), and at all postoperative time points, including at 24 h (1.7 ± 1.7 vs 3.1 ± 1.5, P < 0.05). Morphine requirements in the first 24 postoperative hours were also reduced (21.9 ± 8.9 mg vs 80.4 ± 19.2 mg, P < 0.05). There were no complications attributable to the TAP block. All TAP patients reported high levels of satisfaction with their postoperative analgesic regimen. CONCLUSIONS:The TAP block provided highly effective postoperative analgesia in the first 24 postoperative hours after major abdominal surgery.

The analgesic efficacy of transversus abdominis plane block after cesarean delivery: a randomized controlled trial.

BACKGROUND:The transversus abdominis plane (TAP) block is an effective method of providing postoperative analgesia in patients undergoing midline abdominal wall incisions. We evaluated its analgesic efficacy over the first 48 postoperative hours after cesarean delivery performed through a Pfannensteil incision, in a randomized controlled, double-blind, clinical trial. METHODS:Fifty women undergoing elective cesarean delivery were randomized to undergo TAP block with ropivacaine (n = 25) versus placebo (n = 25), in addition to standard postoperative analgesia comprising patient-controlled IV morphine analgesia and regular diclofenac and acetaminophen. All patients received a standard spinal anesthetic, and at the end of surgery, a bilateral TAP block was performed using 1.5 mg/kg ropivacaine (to a maximal dose of 150 mg) or saline on each side. Each patient was assessed postoperatively by a blinded investigator: in the postanesthesia care unit and at 2, 4, 6, 12, 24, 36, and 48 h postoperatively. RESULTS:The TAP block with ropivacaine compared with placebo reduced postoperative visual analog scale pain scores. Mean (± sd) total morphine requirements in the first 48 postoperative hours were also reduced (66 ± 26 vs 18 ± 14 mg, P < 0.001), as was the 12-h interval morphine consumption up to 36 h postoperatively. The incidence of sedation was reduced in patients undergoing TAP blockade. There were no complications attributable to the TAP block. CONCLUSIONS:The TAP block, as a component of a multimodal analgesic regimen, provided superior analgesia when compared with placebo block up to 48 postoperative hours after elective cesarean delivery.

A comparison of tracheal intubation using the Airtraq or the Macintosh laryngoscope in routine airway management: A randomised, controlled clinical trial.

The Airtraq® laryngoscope is a novel single use tracheal intubation device. We compared the Airtraq® with the Macintosh laryngoscope in patients deemed at low risk for difficult intubation in a randomised, controlled clinical trial. Sixty consenting patients presenting for surgery requiring tracheal intubation were randomly allocated to undergo intubation using a Macintosh (n = 30) or Airtraq® (n = 30) laryngoscope. All patients were intubated by one of four anaesthetists experienced in the use of both laryngoscopes. No significant differences in demographic or airway variables were observed between the groups. All but one patient, in the Macintosh group, was successfully intubated on the first attempt. There was no difference between groups in the duration of intubation attempts. In comparison to the Macintosh laryngoscope, the Airtraq® resulted in modest improvements in the intubation difficulty score, and in ease of use. Tracheal intubation with the Airtraq® resulted in less alterations in heart rate. These findings demonstrate the utility of the Airtraq® laryngoscope for tracheal intubation in low risk patients.

Mesenchymal stem cells enhance recovery and repair following ventilator-induced lung injury in the rat

Background Bone-marrow derived mesenchymal stem cells (MSCs) reduce the severity of evolving acute lung injury (ALI), but their ability to repair the injured lung is not clear. A study was undertaken to determine the potential for MSCs to enhance repair after ventilator-induced lung injury (VILI) and elucidate the mechanisms underlying these effects. Methods Anaesthetised rats underwent injurious ventilation which produced severe ALI. Following recovery, they were given an intravenous injection of MSCs (2×106 cells) or vehicle immediately and a second dose 24 h later. The extent of recovery following VILI was assessed after 48 h. Subsequent experiments examined the potential for non-stem cells and for the MSC secretome to enhance VILI repair. The contribution of specific MSC-secreted mediators was then examined in a wound healing model. Results MSC therapy enhanced repair following VILI. MSCs enhanced restoration of systemic oxygenation and lung compliance, reduced total lung water, decreased lung inflammation and histological lung injury and restored lung structure. They attenuated alveolar tumour necrosis factor α concentrations while increasing concentrations of interleukin 10. These effects were not seen with non-stem cells (ie, rat fibroblasts). MSC-secreted products also enhanced lung repair and attenuated the inflammatory response following VILI. The beneficial effect of the MSC secretome on repair of pulmonary epithelial wounds was attenuated by prior depletion of keratinocyte growth factor. Conclusion MSC therapy enhances lung repair following VILI via a paracrine mechanism that may be keratinocyte growth factor-dependent.

Hypocapnia and the injured brain: more harm than benefit.

Objectives:Hypocapnia is used in the management of acute brain injury and may be life-saving in specific circumstances, but it can produce neuronal ischemia and injury, potentially worsening outcome. This review re-examines the rationale for the use of hypocapnia in acute brain injury and evaluates the evidence for therapeutic and deleterious effects in this context. Data Sources and Study Selection:A MEDLINE/PubMed search from 1966 to August 1, 2009, was conducted using the search terms “hyperventilation,” “hypocapnia,” “alkalosis,” “carbon dioxide,” “brain,” “lung,” and “myocardium,” alone and in combination. Bibliographies of retrieved articles were also reviewed. Data Extraction and Synthesis:Hypocapnia—often for prolonged periods of time—remains prevalent in the management of severely brain-injured children and adults. Despite this, there is no proof beyond clinical experience with incipient herniation that hypocapnia improves neurologic outcome in any context. On the contrary, hypocapnia can cause or worsen cerebral ischemia. The effect of sustained hypocapnia on cerebral blood flow decreases progressively because of buffering; subsequent normocapnia can cause rebound cerebral hyperemia and increase intracranial pressure. Hypocapnia may also injure other organs. Accidental hypocapnia should always be avoided and prophylactic hypocapnia has no current role. Conclusions:Hypocapnia can cause harm and should be strictly limited to the emergent management of life-threatening intracranial hypertension pending definitive measures or to facilitate intraoperative neurosurgery. When it is used, Paco2 should be normalized as soon as is feasible. Outside these settings hypocapnia is likely to produce more harm than benefit.

Ipsilateral transversus abdominis plane block provides effective analgesia after appendectomy in children: a randomized controlled trial.

BACKGROUND:The transversus abdominis plane (TAP) block provides effective postoperative analgesia in adults undergoing major abdominal surgery. Its efficacy in children remains unclear, with no randomized clinical trials in this population. In this study, we evaluated its analgesic efficacy over the first 48 postoperative hours after appendectomy performed through an open abdominal incision, in a randomized, controlled, double-blind clinical trial. METHODS:Forty children undergoing appendectomy were randomized to undergo unilateral TAP block with ropivacaine (n = 19) versus placebo (n = 21) in addition to standard postoperative analgesia comprising IV morphine analgesia and regular diclofenac and acetaminophen. All patients received a standard general anesthetic, and after induction of anesthesia, a TAP block was performed using the landmark technique with 2.5 mg · kg−1 ropivacaine 0.75% or an equal volume (0.3 mL · kg−1) of saline on the ipsilateral side to the incision. RESULTS:The TAP block with ropivacaine reduced mean (±SD) morphine requirements in the first 48 postoperative hours (10.3 ± 12.7 vs 22.3 ± 14.7 mg; P < 0.01) compared with placebo block. The TAP block also reduced postoperative visual analog scale pain scores at rest and on movement compared with placebo. Interval morphine consumption was reduced over the first 24 postoperative hours. There were no between-group differences in the incidence of sedation or nausea and vomiting. There were no complications attributable to the TAP block. CONCLUSIONS:Unilateral TAP block, as a component of a multimodal analgesic regimen, provided superior analgesia compared with placebo in the first 48 postoperative hours after appendectomy in children.

Bench-to-bedside review: Carbon dioxide

Carbon dioxide is a waste product of aerobic cellular respiration in all aerobic life forms. PaCO2 represents the balance between the carbon dioxide produced and that eliminated. Hypocapnia remains a common - and generally underappreciated - component of many disease states, including early asthma, high-altitude pulmonary edema, and acute lung injury. Induction of hypocapnia remains a common, if controversial, practice in both adults and children with acute brain injury. In contrast, hypercapnia has traditionally been avoided in order to keep parameters normal. More recently, advances in our understanding of the role of excessive tidal volume has prompted clinicians to use ventilation strategies that result in hypercapnia. Consequently, hypercapnia has become increasingly prevalent in the critically ill patient. Hypercapnia may play a beneficial role in the pathogenesis of inflammation and tissue injury, but may hinder the host response to sepsis and reduce repair. In contrast, hypocapnia may be a pathogenic entity in the setting of critical illness. The present paper reviews the current clinical status of low and high PaCO2 in the critically ill patient, discusses the insights gained to date from studies of carbon dioxide, identifies key concerns regarding hypocapnia and hypercapnia, and considers the potential clinical implications for the management of patients with acute lung injury.

Clinical grade allogeneic human mesenchymal stem cells restore alveolar fluid clearance in human lungs rejected for transplantation

The lack of suitable donors for all solid-organ transplant programs is exacerbated in lung transplantation by the low utilization of potential donor lungs, due primarily to donor lung injury and dysfunction, including pulmonary edema. The current studies were designed to determine if intravenous clinical-grade human mesenchymal stem (stromal) cells (hMSCs) would be effective in restoring alveolar fluid clearance (AFC) in the human ex vivo lung perfusion model, using lungs that had been deemed unsuitable for transplantation and had been subjected to prolonged ischemic time. The human lungs were perfused with 5% albumin in a balanced electrolyte solution and oxygenated with continuous positive airway pressure. Baseline AFC was measured in the control lobe and if AFC was impaired (defined as <10%/h), the lungs received either hMSC (5 × 10(6) cells) added to the perfusate or perfusion only as a control. AFC was measured in a different lung lobe at 4 h. Intravenous hMSC restored AFC in the injured lungs to a normal level. In contrast, perfusion only did not increase AFC. This positive effect on AFC was reduced by intrabronchial administration of a neutralizing antibody to keratinocyte growth factor (KGF). Thus, intravenous allogeneic hMSCs are effective in restoring the capacity of the alveolar epithelium to remove alveolar fluid at a normal rate, suggesting that this therapy may be effective in enhancing the resolution of pulmonary edema in human lungs deemed clinically unsuitable for transplantation.

Effects of Intratracheal Mesenchymal Stromal Cell Therapy during Recovery and Resolution after Ventilator-induced Lung Injury

Background:Mesenchymal stromal cells (MSCs) have been demonstrated to attenuate acute lung injury when delivered by intravenous or intratracheal routes. The authors aimed to determine the efficacy of and mechanism of action of intratracheal MSC therapy and to compare their efficacy in enhancing lung repair after ventilation-induced lung injury with intravenous MSC therapy. Methods:After induction of anesthesia, rats were orotracheally intubated and subjected to ventilation-induced lung injury (respiratory rate 18 min−1, Pinsp 35 cm H2O,) to produce severe lung injury. After recovery, animals were randomized to receive: (1) no therapy, n = 4; (2) intratracheal vehicle (phosphate-buffered saline, 300 µl, n = 8); (3) intratracheal fibroblasts (4 × 106 cells, n = 8); (4) intratracheal MSCs (4 × 106 cells, n = 8); (5) intratracheal conditioned medium (300 µl, n = 8); or (6) intravenous MSCs (4 × 106 cells, n = 4). The extent of recovery after acute lung injury and the inflammatory response was assessed after 48 h. Results:Intratracheal MSC therapy enhanced repair after ventilation-induced lung injury, improving arterial oxygenation (mean ± SD, 146 ± 3.9 vs. 110.8 ± 21.5 mmHg), restoring lung compliance (1.04 ± 0.11 vs. 0.83 ± 0.06 ml·cm H2O−1), reducing total lung water, and decreasing lung inflammation and histologic injury compared with control. Intratracheal MSC therapy attenuated alveolar tumor necrosis factor-&agr; (130 ± 43 vs. 488 ± 211 pg·ml−1) and interleukin-6 concentrations (138 ± 18 vs. 260 ± 82 pg·ml−1). The efficacy of intratracheal MSCs was comparable with intravenous MSC therapy. Intratracheal MSCs seemed to act via a paracine mechanism, with conditioned MSC medium also enhancing lung repair after injury. Conclusions:Intratracheal MSC therapy enhanced recovery after ventilation-induced lung injury via a paracrine mechanism, and was as effective as intravenous MSC therapy.

Hypercapnic acidosis attenuates ventilation-induced lung injury by a nuclear factor-κB-dependent mechanism.

Objectives:Hypercapnic acidosis protects against ventilation-induced lung injury. We wished to determine whether the beneficial effects of hypercapnic acidosis in reducing stretch-induced injury were mediated via inhibition of nuclear factor-&kgr;B, a key transcriptional regulator in inflammation, injury, and repair. Design:Prospective randomized animal study. Setting:University research laboratory. Subjects:Adult male Sprague-Dawley rats. Interventions:In separate experimental series, the potential for hypercapnic acidosis to attenuate moderate and severe ventilation-induced lung injury was determined. In each series, following induction of anesthesia and tracheostomy, Sprague-Dawley rats were randomized to (normocapnia; FICO2 0.00) or (hypercapnic acidosis; FICO2 0.05), subjected to high stretch ventilation, and the severity of lung injury and indices of activation of the nuclear factor-&kgr;B pathway were assessed. Subsequent in vitro experiments examined the potential for hypercapnic acidosis to reduce pulmonary epithelial inflammation and injury induced by cyclic mechanical stretch. The role of the nuclear factor-&kgr;B pathway in hypercapnic acidosis–mediated protection from stretch injury was then determined. Measurements and Main Results:Hypercapnic acidosis attenuated moderate and severe ventilation-induced lung injury, as evidenced by improved oxygenation, compliance, and reduced histologic injury compared to normocapnic conditions. Hypercapnic acidosis reduced indices of inflammation such as interleukin-6 and bronchoalveolar lavage neutrophil infiltration. Hypercapnic acidosis reduced the decrement of the nuclear factor-&kgr;B inhibitor I&kgr;B&agr; and reduced the generation of cytokine-induced neutrophil chemoattractant-1. Hypercapnic acidosis reduced cyclic mechanical stretch-induced nuclear factor-&kgr;B activation, reduced interleukin-8 production, and decreased epithelial injury and cell death compared to normocapnia. Conclusions:Hypercapnic acidosis attenuated ventilation-induced lung injury independent of injury severity and decreased mechanical stretch-induced epithelial injury and death, via a nuclear factor-&kgr;B–dependent mechanism.