Patrick Hassett

Preoperative Intravenous Fluid Therapy Decreases Postoperative Nausea and Pain in High Risk Patients

The potential for preoperative IV rehydration to reduce postoperative nausea and vomiting (PONV) and pain in patients undergoing ambulatory surgery remains unclear, with conflicting results reported. We sought to determine whether preoperative IV rehydration with a balanced salt solution would decrease the incidence of PONV in patients at increased risk for these symptoms. Eighty ASA grade I–III patients presenting for gynecologic laparoscopy were randomized to receive large (2 mL/kg per hour fasting) or small (3 mL/kg) volume infusions of compound sodium lactate solution over 20 min preoperatively. A standardized balanced anesthetic was used. The incidence and severity of PONV and pain, and need for supplemental antiemetic and analgesic therapy, were assessed by a blinded investigator at 0.5, 1, and 4 h postoperatively, and on the first and third postoperative days. The incidence (control 87% versus large volume 59%) and severity of PONV were significantly reduced in the large volume infusion group at all time intervals. The large volume infusion group also had decreased postoperative pain scores and required less supplemental analgesia. Preoperative correction of intravascular volume deficits effectively reduces PONV and postoperative pain in high risk patients presenting for ambulatory surgery. We recommend the preoperative administration of 2 mL/kg of compound sodium lactate for every hour of fasting to patients with an increased PONV risk presenting for ambulatory surgery.

Hypercapnic acidosis attenuates pulmonary epithelial wound repair by an NF-κB dependent mechanism

Background: Hypercapnic acidosis exerts protective effects in acute lung injury but may also slow cellular repair. These effects may be mediated via inhibition of nuclear factor-κB (NF-κB), a pivotal transcriptional regulator in inflammation and repair. Objectives: To determine the effects of hypercapnic acidosis in pulmonary epithelial wound repair, to elucidate the role of NF-κB and to examine the mechanisms by which these effects are mediated. Methods: Confluent small airway epithelial cell, human bronchial epithelial cell and type II alveolar A549 cell monolayers were subjected to wound injury under conditions of hypercapnic acidosis (pH 7.0, carbon dioxide tension (Pco2) 11 kPa) or normocapnia (pH 7.37, Pco2 5.5 kPa) and the rate of healing determined. Subsequent experiments investigated the role of hypercapnia versus acidosis and elucidated the role of NF-κB and mitogen-activated protein kinases. The roles of cellular mitosis versus migration and of matrix metalloproteinases in mediating these effects were then determined. Results: Hypercapnic acidosis reduced wound closure (mean (SD) 33 (6.3)% vs 64 (5.9)%, p<0.01) and reduced activation of NF-κB compared with normocapnia. Buffering of the acidosis did not alter this inhibitory effect. Prior inhibition of NF-κB activation occluded the effect of hypercapnic acidosis. Inhibition of ERK, JNK and P38 did not modulate wound healing. Hypercapnic acidosis reduced epithelial cell migration but did not alter mitosis, and reduced matrix metalloproteinase-1 while increasing concentrations of tissue inhibitor of metalloproteinase-2. Conclusions: Hypercapnic acidosis inhibits pulmonary epithelial wound healing by reducing cell migration via an NF-κB dependent mechanism that may involve alterations in matrix metalloproteinase activity.

Hypercapnic acidosis attenuates shock and lung injury in early and prolonged systemic sepsis

Objective:To investigate whether acute hypercapnic acidosis—induced by adding CO2 to inspired gas—would protect against severe systemic sepsis-induced lung and systemic organ injury resulting from cecal ligation and puncture. Acute hypercapnic acidosis protects against lung injury after both nonseptic and early pneumonia-induced lung injury. In contrast, prolonged hypercapnia worsens pneumonia-induced lung injury. The effects of hypercapnia and acidosis in the setting of systemic sepsis remain to be determined. Design:Prospective randomized animal study. Setting:University research laboratory. Subjects:Adult male Sprague-Dawley rats. Interventions:In the early systemic sepsis series, post induction of anesthesia and tracheostomy placement, animals were randomized to normocapnia (Fico2 = 0.00, n = 12) or hypercapnic acidosis (Fico2 = 0.05, n = 12). Cecal ligation and puncture were performed and the animals were ventilated for 3 hrs. In the prolonged systemic sepsis series, rats were anesthetized, cecal ligation and puncture were performed, and the animals were allowed to recover. The animals were then randomized to housing under conditions of environmental normocapnia (Fico2 = 0.00, n = 20) or hypercapnia (Fico2 = 0.08, n = 20). After 96 hrs, the animals were reanesthetized, and the severity of lung and hemodynamic injury was assessed. Results:In early systemic sepsis, hypercapnic acidosis attenuated the development and severity of hypotension, and reduced lactate accumulation and the decrement in central venous oxyhemoglobin levels, compared with normocapnia. Hypercapnic acidosis reduced bronchoalveolar lavage neutrophil infiltration, and lung wet/dry weight ratios. In prolonged systemic sepsis, hypercapnic acidosis reduced histologic indices of lung injury. There was no evidence that hypercapnia worsened prolonged systemic sepsis-induced lung injury. Hypercapnic acidosis did not alter lung or systemic bacterial loads in early or prolonged systemic sepsis. Conclusion:Hypercapnic acidosis exerts beneficial effects in early and prolonged cecal ligation and puncture-induced polymicrobial systemic sepsis.

A comparison of the Glidescope®, Pentax AWS®, and Macintosh laryngoscopes when used by novice personnel: a manikin study

PurposeDirect laryngoscopic tracheal intubation is a potentially lifesaving procedure, but a difficult skill to acquire and maintain. The consequences of poorly performed intubation attempts are potentially severe. The Pentax AWS® and the Glidescope® are indirect laryngoscopes that may require less skill to use. We therefore hypothesized that AWS® and Glidescope® would prove superior to the Macintosh laryngoscope when used by novices in the normal and simulated difficult airway.MethodsIn this prospective randomized crossover trial following standardized didactic instruction, medical students with no prior experience of laryngoscopy performed tracheal intubation using each device. Each student was allowed up to three attempts to intubate in a Laerdal® Intubation Trainer in two laryngoscopy scenarios and in a Laerdal® SimMan® manikin in one scenario. The students then performed tracheal intubation of the normal airway a second time to characterize the learning curve for each device.ResultsThe Pentax AWS® provided better intubation conditions than the Glidescope® or the Macintosh, resulting in greater success of intubation, particularly in the difficult laryngoscopy scenarios. The Glidescope® demonstrated advantages over the Macintosh, particularly in the more difficult scenarios. Both the AWS® and the Glidescope® decreased the duration of intubation attempts, reduced the number of maneuvers required, and reduced the potential for dental trauma. In direct comparisons, the AWS® provided the best intubation conditions.ConclusionsThe Pentax AWS® appears to constitute a better alternative to the Macintosh for novice personnel to acquire the skills of tracheal intubation.RésuméObjectifL’intubation trachéale par laryngoscopie directe est une procédure potentiellement salutaire, mais il s’agit également d’une compétence difficile à acquérir et à maintenir. Les conséquences de tentatives d’intubation mal réalisées sont potentiellement graves. Le Pentax AWS® et le Glidescope® sont des laryngoscopes indirects qui pourraient nécessiter une compétence moindre. Ainsi, nous avons émis l’hypothèse que l’AWS® et le Glidescope® donneraient de meilleurs résultats que le laryngoscope Macintosh lors de leur utilisation par du personnel inexpérimenté pour l’intubation de voies aériennes normales ou rendues difficiles par simulation.MéthodeDans cette étude croisée randomisée et prospective qui a été menée à la suite d’une formation didactique standard, des étudiants en médecine n’ayant pas d’expérience antérieure en matière de laryngoscopie ont réalisé une intubation trachéale à l’aide de chacun des appareils. Chaque étudiant avait droit à un maximum de trois tentatives d’intubation sur un simulateur d’intubation Laerdal® dans le cadre de deux scénarios de laryngoscopie, dont l’un sur un mannequin Laerdal® SimMan®. Les étudiants ont ensuite réalisé une seconde intubation trachéale dans une voie aérienne normale afin de déterminer la courbe d’apprentissage de chaque appareil.RésultatsLe Pentax AWS® a procuré de meilleures conditions d’intubation que le Glidescope® ou le Macintosh, ce qui a eu pour résultat un taux de réussite de l’intubation plus élevé et ce, particulièrement dans les situations de laryngoscopie difficile. Le Glidescope® a démontré des avantages par rapport au Macintosh, notamment dans les situations de laryngoscopie plus difficile. L’AWS® et le Glidescope® ont permis de réduire la durée des tentatives d’intubation, le nombre de manœuvres nécessaires, ainsi que le potentiel d’un traumatisme dentaire. En comparaison directe, l’AWS® était le laryngoscope procurant les meilleures conditions d’intubation.ConclusionLe laryngoscope Pentax AWS® semble constituer une meilleure alternative au Macintosh pour permettre au personnel inexpérimenté d’acquérir les compétences nécessaires à l’intubation trachéale.

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.

Differential Effects of Buffered Hypercapnia versus Hypercapnic Acidosis on Shock and Lung Injury Induced by Systemic Sepsis

Background:Acute hypercapnic acidosis protects against lung injury caused by nonseptic insults and after both pulmonary and systemic sepsis. The authors wished to dissect the contribution of the acidosis versus hypercapnia per se to the effects of hypercapnic acidosis on the hemodynamic profile and severity of lung injury induced by systemic sepsis. Methods:In the hypercapnic acidosis series, adult male Sprague-Dawley rats were randomized to normocapnia or hypercapnic acidosis—produced by adding 5% carbon dioxide to the inspired gas—and cecal ligation and puncture performed. In the buffered hypercapnia series, animals were first randomized to housing under conditions of environmental normocapnia or hypercapnia—produced by exposure to 8% carbon dioxide—to allow renal buffering. After 96 h, cecal ligation and puncture was performed. In both series, the animals were ventilated for 6 h, and the severity of the lung injury and hemodynamic deterioration were assessed. Results:Both hypercapnic acidosis and buffered hypercapnia attenuated the development and severity of hypotension and reduced lactate accumulation compared to normocapnia. Hypercapnic acidosis reduced lung injury and inflammation, decreased mean (± SD) bronchoalveolar lavage protein concentration (232 ± 50 versus 279 ± 27 μg · ml−1) and median neutrophil counts (3,370 versus 9,120 cells · ml−1), and reduced histologic lung injury. In contrast, buffered hypercapnia did not reduce the severity of systemic sepsis induced lung injury. Conclusions:Both hypercapnic acidosis and buffered hypercapnia attenuate the hemodynamic consequences of systemic sepsis. In contrast, hypercapnic acidosis, but not buffered hypercapnia, reduced the severity of sepsis-induced lung injury.

Determination Of The Efficacy And Side-effect Profile Of Lower Doses Of Intrathecal Morphine In Patients Undergoing Total Knee Arthroplasty.

BackgroundIntrathecal (IT) morphine provides excellent post-operative analgesia, but causes multiple side effects including nausea and vomiting (PONV), pruritus and respiratory depression, particularly at higher doses. The lowest effective dose of spinal morphine in patients undergoing total knee arthroplasty is not known.MethodsWe evaluated the analgesic efficacy and side effect profile of 100 – 300 μg IT morphine in patients undergoing elective total knee replacement in this prospective, randomized, controlled, double-blind study. Sixty patients over the age of 60 undergoing elective knee arthroplasty were enrolled. Patients were randomized to receive spinal anaesthesia with 15 mg Bupivacaine and IT morphine in three groups: (i) 100 μg; (ii) 200 μg; and (iii) 300 μg.ResultsBoth 200 μg and 300 μg IT morphine provided comparable levels of postoperative analgesia. However, patients that received 100 μg had greater pain postoperatively, with higher pain scores and a greater requirement for supplemental morphine. There were no differences between groups with regard to PONV, pruritus, sedation, respiratory depression or urinary retention.ConclusionBoth 200 μg and 300 μg provided comparable postoperative analgesia, which was superior to that provided by 100 μg IT morphine in patients undergoing total knee arthroplasty. Based on these findings, we recommend that 200 μg IT morphine be used in these patients.Trial registrationClinicalTrials.gov Identifier NCT00695045

Hypercapnia: Permissive, Therapeutic, or Not at All?

In the past, hypercapnia and its concomitant hypercapnic acidosis, have been considered to be adverse, and were strictly avoided in the critically ill. Support for this approach derived from concerns regarding the link between hypercapnia and/or acidosis and adverse outcome in diverse clinical contexts, including cardiac arrest, sepsis, and neonatal asphyxia [1]. However, accumulating evidence from experimental and clinical studies demonstrates the potential for mechanical ventilation to directly injure the lungs — a phenomenon termed ‘ventilator-induced lung injury (VILI)’ — and has mandated a rethink of our approaches to hypercapnia.