Brian P. Kavanagh

Preemptive analgesia. Clinical evidence of neuroplasticity contributing to postoperative pain.

Recent evidence suggests that surgical incision and other noxious perioperative events may induce prolonged changes in central neural function that later contribute to postoperative pain. The present study tested the hypothesis that patients receiving epidural fentanyl before incision would have less pain and need fewer analgesics post-operatively than patients receiving the same dose of epidural fentanyl after incision. Thirty patients (ASA physical status 2) scheduled for elective thoracic surgery through a posterolateral thoracotomy incision were randomized to one of two groups of equal size and prospectively studied in a double-blind manner. Epidural catheters were placed via the L2-L3 or L3-L4 interspaces preoperatively, and the position was confirmed with lidocaine. Group 1 received epidural fentanyl (4 micrograms/kg, in 20 ml normal saline) before surgical incision, followed by epidural normal saline (20 ml) infused 15 min after incision. Group 2 received epidural normal saline (20 ml) before surgical incision, followed by epidural fentanyl (4 micrograms/kg, in 20 ml normal saline) infused 15 min after incision. No additional analgesics were used before or during the operation. Anesthesia was induced with thiopental (3-5 mg/kg) and maintained with N2O/O2 and isoflurane. Paralysis was achieved with pancuronium (0.1 mg/kg). Postoperative analgesia consisted of patient-controlled intravenous morphine. Visual analogue scale pain scores were significantly less in group 1 (2.6 +/- 0.44) than in group 2 (4.7 +/- 0.58) 6 h after surgery (P less than 0.05), by which time plasma fentanyl concentrations had decreased to subtherapeutic levels (less than 0.15 ng/ml) in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary atelectasis : A pathogenic perioperative entity

Atelectasis occurs in the dependent parts of the lungs of most patients who are anesthetized. Development of atelectasis is associated with decreased lung compliance, impairment of oxygenation, increased pulmonary vascular resistance, and development of lung injury. The adverse effects of atelectasis persist into the postoperative period and can impact patient recovery. This review article focuses on the causes, nature, and diagnosis of atelectasis. The authors discuss the effects and implications of atelectasis in the perioperative period and illustrate how preventive measures may impact outcome. In addition, they examine the impact of atelectasis and its prevention in acute lung injury.

Protocolized intensive care unit management of analgesia, sedation, and delirium improves analgesia and subsyndromal delirium rates.

BACKGROUND: Sedatives and analgesics, in doses that alter consciousness in the intensive care unit (ICU), contribute to delirium and mortality. Pain, agitation, and delirium can be monitored in ICU patients. These symptoms were noted before (PRE) and after (POST) a protocol to alleviate undesirable symptoms. Analgesia and sedation levels, the incidence of coma, delirium, length of stay (LOS), discharge location, and mortality were then compared. We hypothesized that the likely reduction in iatrogenic coma would result in less delirium, because these 2 morbid conditions seem to be linked. METHODS: All patients were consecutively admitted to an ICU PRE-protocol (August 2003 to February 2004, 610 patients) and POST-protocol (April 2005 to November 2005, 604 patients). Between February 2004 and April 2005, we piloted and taught individualized nonpharmacologic strategies and titration of analgesics, sedatives, and antipsychotics based on sedation, analgesia, and delirium scores. We measured the following outcomes: coma, delirium, LOS, mortality, and discharge location. RESULTS: The POST group benefited from better analgesia, received less opiates (90.72 ± 207.45 vs 22.93 ± 40.36 morphine equivalents/d, P = <0.0001), and, despite comparable sedation, had shorter duration of mechanical ventilation. Medication-induced coma rates (18.1%vs 7.2%, P < 0.0001), ICU and hospital LOS, and dependency at discharge were lower in the POST-protocol group. Subsyndromal delirium was significantly reduced; delirium was similar. The 30-day mortality risk in the PRE cohort was 29.4% vs 22.9% in the POST cohort (log-rank test, P = 0.009). CONCLUSION: Educational initiatives incorporating systematic management protocols with nonpharmacologic measures and individualized titration of sedation, analgesia, and delirium therapies are associated with better outcomes.

Carbon dioxide and the critically ill--too little of a good thing?

Permissive hypercapnia (acceptance of raised concentrations of carbon dioxide in mechanically ventilated patients) may be associated with increased survival as a result of less ventilator-associated lung injury. Conversely, hypocapnia is associated with many acute illnesses (eg, asthma, systemic inflammatory response syndrome, pulmonary oedema), and is thought to reflect underlying hyperventilation. Accumulating clinical and basic scientific evidence points to an active role for carbon dioxide in organ injury, in which raised concentrations of carbon dioxide are protective, and low concentrations are injurious. We hypothesise that therapeutic hypercapnia might be tested in severely ill patients to see whether supplemental carbon dioxide could reduce the adverse effects of hypocapnia and promote the beneficial effects of hypercapnia. Such an approach could also expand our understanding of the pathogenesis of disorders in which hypocapnia is a constitutive element.

Spontaneous Effort Causes Occult Pendelluft during Mechanical Ventilation

RATIONALE In normal lungs, local changes in pleural pressure (P(pl)) are generalized over the whole pleural surface. However, in a patient with injured lungs, we observed (using electrical impedance tomography) a pendelluft phenomenon (movement of air within the lung from nondependent to dependent regions without change in tidal volume) that was caused by spontaneous breathing during mechanical ventilation. OBJECTIVES To test the hypotheses that in injured lungs negative P(pl) generated by diaphragm contraction has localized effects (in dependent regions) that are not uniformly transmitted, and that such localized changes in P(pl) cause pendelluft. METHODS We used electrical impedance tomography and dynamic computed tomography (CT) to analyze regional inflation in anesthetized pigs with lung injury. Changes in local P(pl) were measured in nondependent versus dependent regions using intrabronchial balloon catheters. The airway pressure needed to achieve comparable dependent lung inflation during paralysis versus spontaneous breathing was estimated. MEASUREMENTS AND MAIN RESULTS In all animals, spontaneous breathing caused pendelluft during early inflation, which was associated with more negative local P(pl) in dependent regions versus nondependent regions (-13.0 ± 4.0 vs. -6.4 ± 3.8 cm H2O; P < 0.05). Dynamic CT confirmed pendelluft, which occurred despite limitation of tidal volume to less than 6 ml/kg. Comparable inflation of dependent lung during paralysis required almost threefold greater driving pressure (and tidal volume) versus spontaneous breathing (28.0 ± 0.5 vs. 10.3 ± 0.6 cm H2O, P < 0.01; 14.8 ± 4.6 vs. 5.8 ± 1.6 ml/kg, P < 0.05). CONCLUSIONS Spontaneous breathing effort during mechanical ventilation causes unsuspected overstretch of dependent lung during early inflation (associated with reciprocal deflation of nondependent lung). Even when not increasing tidal volume, strong spontaneous effort may potentially enhance lung damage.

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.

Pre-emptive lumbar epidural anaesthesia reduces postoperative pain and patient-controlled morphine consumption after lower abdominal surgery

&NA; The present study tested the hypothesis that patients receiving epidural bupivacaine before surgery would require less morphine postoperatively and/or report less intense pain than patients receiving epidural bupivacaine after incision but before the end of surgery. Forty‐two patients (ASA class I‐III) scheduled for lower abdominal surgery were randomly assigned to 1 of 2 groups of equal size and prospectively studied using a double‐blind, placebo‐controlled crossover design. Epidural catheters were placed in the T12‐L1 or L1‐L2 interspaces pre‐operatively, the position of the catheter was confirmed with 3% chloroprocaine with epinephrine 1:200,000, and sensory testing was carried out until levels had receded to below T12. Group 1 received 15 ml of 0.5% epidural bupivacaine injected 35 min before incision followed by 15 ml of epidural normal saline 30 min after incision. Group 2 received 15 ml of epidural normal saline injected 37 min before incision followed by 15 ml of 0.5% epidural bupivacaine 30 min after incision. General anaesthesia was induced with thiopental (4–6 mg/kg) and maintained with N2O/O2 and isoflurane. Paralysis was achieved with pancuronium (0.1 mg/kg). Opioids were not used as pre‐medication or during surgery. Postoperative analgesia consisted of patient‐controlled (PCA) intravenous morphine. Visual analogue pain scores (VAS) (at rest and after standardized mobilization) did not differ significantly between the 2 groups but McGill Pain Questionnaire (MPQ) pain ratings were significantly lower in group 1 at the 24 and 72 h assessments. Group 1 used significantly less morphine than did group 2 between 12 and 24 h after surgery. Cumulative PCA morphine consumption in group 1 (55.2 ± 4.7 mg) was significantly lower than in group 2 (71.7 ± 6.1 mg) 24 h and 48 h (group 1: 86.8 ± 6.3 mg vs. group 2: 108.9 ± 9.8 mg) after surgery, but not at the 72 h assessment. Reduction in morphine dose at 24, 48 and 72 h amounted to 30%, 25% and 22%, respectively. The results suggest that single‐shot pre‐emptive epidural local anaesthesia is associated with a short‐term morphine‐sparing effect which is most pronounced between 12 and 24 h after surgery. Extending the pre‐operative blockade into the postoperative period may prolong the initial advantage conferred by pre‐emptive epidural local anaesthesia.

Epidural Bupivacaine-Morphine Analgesia versus Patient-controlled Analgesia following Abdominal Aortic Surgery: Analgesic, Respiratory, and Myocardial Effects

Background The efficacy and effects of epidural analgesia compared with patient-controlled analgesia (PCA) have not been reported in patients undergoing major vascular surgery. We compared the effects of epidural bupivacaine-morphine with those of intravenous PCA morphine after elective infrarenal aortic surgery. Methods Forty patients classified as American Society of Anesthesiologists physical status 2 or 3 received general anesthesia plus postoperative PCA using morphine sulfate (group PCA; n = 21) or general anesthesia plus perioperative epidural morphine - bupivacaine (group EPI; n = 19) during a period of 48 h. During operation, EPI patients received 0.05 mg/kg epidural morphine and 5 ml 0.25% bupivacaine followed by an infusion of 0.125% bupivacaine with 0.1% morphine (0.1 mg/ml); group PCA received 0.1 mg/kg intravenous morphine sulfate. Continuous electrocardiographic monitoring (V4 and V5 leads) was performed from the night before surgery until 48 h afterward. Respiratory inductive plethysmographic data were recorded after tracheal extubation. Visual analog pain scores at rest and after movement were performed every 4 h after extubation. Results Nurse-administered intravenous morphine and time to tracheal extubation were less in group EPI, as were visual analog pain scores at rest and after movement from 20 to 48 h. Complications and the duration of intensive care unit and hospital stay were comparable. There was a similar, low incidence of postoperative apneas, slow respiratory rates, desaturation, and S-T segment depression. Conclusions Epidural morphine-bupivacaine is associated with reduced early postoperative intravenous opioid requirements, more rapid tracheal extubation, and superior analgesia after abdominal aortic surgery, with comparable respiratory effects.

Evolution of Diaphragm Thickness during Mechanical Ventilation. Impact of Inspiratory Effort

RATIONALE Diaphragm atrophy and dysfunction have been reported in humans during mechanical ventilation, but the prevalence, causes, and functional impact of changes in diaphragm thickness during routine mechanical ventilation for critically ill patients are unknown. OBJECTIVES To describe the evolution of diaphragm thickness over time during mechanical ventilation, its impact on diaphragm function, and the influence of inspiratory effort on this phenomenon. METHODS In three academic intensive care units, 107 patients were enrolled shortly after initiating ventilation along with 10 nonventilated intensive care unit patients (control subjects). Diaphragm thickness and contractile activity (quantified by the inspiratory thickening fraction) were measured daily by ultrasound. MEASUREMENTS AND MAIN RESULTS Over the first week of ventilation, diaphragm thickness decreased by more than 10% in 47 (44%), was unchanged in 47 (44%), and increased by more than 10% in 13 (12%). Thickness did not vary over time following extubation or in nonventilated patients. Low diaphragm contractile activity was associated with rapid decreases in diaphragm thickness, whereas high contractile activity was associated with increases in diaphragm thickness (P = 0.002). Contractile activity decreased with increasing ventilator driving pressure (P = 0.01) and controlled ventilator modes (P = 0.02). Maximal thickening fraction (a measure of diaphragm function) was lower in patients with decreased or increased diaphragm thickness (n = 10) compared with patients with unchanged thickness (n = 10; P = 0.05 for comparison). CONCLUSIONS Changes in diaphragm thickness are common during mechanical ventilation and may be associated with diaphragmatic weakness. Titrating ventilatory support to maintain normal levels of inspiratory effort may prevent changes in diaphragm configuration associated with mechanical ventilation.

Anesthetic technique and the cytokine and matrix metalloproteinase response to primary breast cancer surgery.

Background: Breast cancer is the most common malignancy in women. Surgery remains the most effective treatment. Several perioperative factors, including the surgical stress response, many anesthetics and opioids, adversely affect immune function. Regional anesthesia-analgesia attenuates perioperative immunosuppression. We tested the hypothesis that patients who receive combined propofol/paravertebral anesthesia-analgesia (propofol/paravertebral) exhibited reduced levels of protumorigenic cytokines and matrix metalloproteinases (MMPs) and elevated levels of antitumorigenic cytokines compared with patients receiving sevoflurane anesthesia with opioid analgesia (sevoflurane/opioid). Methods: Primary breast cancer surgery patients were randomized to propofol/paravertebral (n = 15) or sevoflurane/opioid (n = 17) and preoperative and postoperative serum concentrations of 11 cytokines (interleukin 1&bgr; [IL-1&bgr;], IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon &ggr;, and tumor necrosis factor &agr;) and 3 MMPs (MMP-1, MMP-3, and MMP-9) were measured. Results: Treatment groups were well balanced for age, weight, surgical procedure, and cancer pathologic diagnosis. Pain scores were lower at 1 and 2 hrs with paravertebral analgesia compared with morphine but similar at 24 hrs. Patients in the propofol/paravertebral group showed a greater percentage decrease in postoperative compared with preoperative IL-1&bgr; (median [quartiles], −26% [−15% to −52%] versus −4% [−14% to 2%], P = 0.003), a significant attenuation in elevated MMP-3 (2% [−39% to 12%] versus 29% [23%-59%], P = 0.011) and MMP-9 (26% [13%-54%] versus 74% [50%-108%], P = 0.02), and a significant increase in IL-10 (10% [5%-33%] versus −15% [20% to −2%], P = 0.001) compared with sevoflurane/opioid group. No significantly different changes in IL-2, IL-4, IL-5, IL-6, IL-8, IL-12p70, IL-13, interferon &ggr;, tumor necrosis factor &agr;, or MMP-1 were observed between the 2 groups. Conclusions: Propofol/paravertebral anesthesia-analgesia for breast cancer surgery alters a minority of cytokines influential in regulating perioperative cancer immunity. Further evaluation is required to determine the significance of these observations.