George D. Shorten

Perioperative Intravenous Lidocaine Decreases the Incidence of Persistent Pain After Breast Surgery

Objectives: Breast cancer surgery is associated with a high incidence of persistent postsurgical pain (PPSP). The aim of this study was to evaluate the impact of intravenous (IV) lidocaine on acute and PPSP, analgesic requirements, and sensation abnormalities in patients undergoing surgery for breast cancer. Methods: Thirty-six patients participated in this randomized, double-blinded study. Before induction of general anesthesia, patients received a bolus of intravenous lidocaine 1.5 mg/kg followed by a continuous infusion of lidocaine 1.5 mg/kgh (lidocaine group) or an equal volume of saline (control group). The infusion was stopped 1 hour after the skin closure. Pain scores and analgesic consumption were recorded at 2, 4, 24 hours, and then daily for 1 week postoperatively. Three months later, patients were assessed for PPSP and secondary hyperalgesia. Results: Two (11.8%) patients in the lidocaine group and 9 (47.4%) patients in the control group reported PPSP at 3 months follow-up (P=0.031). McGill Pain Questionnaire revealed greater present pain intensity-visual analog scale in the control group (14.6±22.5 vs. 2.6±7.5; P=0.025). Secondary hyperalgesia (area of hyperalgesia/length of surgical incision) was significantly less in the lidocaine group compared with control group (0.2±0.8 vs. 3.2±4.5 cm; P=0.002). The 2 groups were similar in terms of analgesic consumption during the early postoperative period. Discussion: Intravenous perioperative lidocaine decreases the incidence and severity of PPSP after breast cancer surgery. Prevention of the induction of central hyperalgesia is a potential mechanism.

Radiologic Localization of the Laryngeal Mask Airway in Children

In the absence of data on the anatomic localization of the cuff of the laryngeal mask airway (LMA) in children, radiologic images were obtained from 50 infants and children (aged 1 month to 15 yr) undergoing diagnostic radiologic procedures during halothane and N2O:O2 anesthesia. In 46 patients, the cuff of the LMA was in the pharynx and covered the laryngeal opening. The upper (proximal) section was adjacent to the base of the tongue at the level of C1 or C2 vertebrae pushing the tongue forward and its lower (distal) end was in the inferior recesses of the hypopharynx at the levels of C4 to T1 vertebrae. The cuff of LMA at this position between the base of the tongue above the epiglottis and below the laryngeal opening, covered the laryngeal aperture, forming a low pressure seal at the entrance of the larynx. In 37 of these 46 patients, a posterior deflection of the epiglottis was noted (< 45 degrees), and in only 9, the epiglottis was in the anatomic position. In four patients, the cuff of the LMA was located in the oropharynx. No correlation was found between the size of the LMA and the position of the epiglottis with respect to end-tidal CO2, respiratory rate, or the leak pressures. The size of the LMA, its anatomic location, and the position of the epiglottis had no significant effect on the respiratory parameters of spontaneously breathing children.

Perioperative pregabalin improves pain and functional outcomes 3 months after lumbar discectomy.

BACKGROUND:Patient outcome after lumbar discectomy for radicular low back pain is variable and the benefit is inconsistent. Many patients continue to experience pain 3 months after surgery. Pregabalin, a membrane stabilizer, may decrease perioperative central sensitization and subsequent persistent pain. METHODS:Forty patients undergoing lumbar discectomy were randomly allocated to receive either pregabalin (300 mg at 90 minutes preoperatively and 150 mg at 12 and 24 hours postoperatively) or placebo at corresponding times in a double-blinded manner. Our primary outcome was the change in the present pain intensity (PPI) (visual analog scale [VAS], 0–100 mm [PPI-VAS, McGill Pain Questionnaire]) from preoperatively to 3 months postoperatively. RESULTS:The decrease in PPI-VAS score at 3 months was greater in patients who received pregabalin (37.6 ± 19.6 mm) (mean ± SD) than those who received placebo (25.3 ± 21.9 mm) (P = 0.08). The Roland Morris disability score at 3 months was less in patients who received pregabalin (2.7 ± 2.4) than in those who received placebo (5.6 ± 4.8) (P = 0.032). Pregabalin administration was associated with greater pain tolerance thresholds in both lower limbs compared with placebo at 24 hours postoperatively. CONCLUSION:Perioperative pregabalin administration is associated with less pain intensity and improved functional outcomes 3 months after lumbar discectomy.

The effects of fenoldopam on renal function in patients undergoing elective aortic surgery.

BACKGROUND AND OBJECTIVE Postoperative renal impairment is a recognized complication of infrarenal aortic cross-clamping. Our hypothesis was that the renal vasodilating and natriuretic effects of fenoldopam mesylate, a selective dopamine (DA1) agonist, would preserve renal function in patients undergoing elective infrarenal aortic cross-clamping. METHODS A prospective, randomized, double blind controlled clinical trial was performed. Twenty-eight ASA II-III patients undergoing elective aortic surgery requiring infrarenal aortic cross-clamping were studied. According to random allocation, patients received either fenoldopam (0.1 microg kg(-1) min(-1)) or placebo intravenously prior to surgical skin incision until release of the aortic clamp. Plasma creatinine, creatinine clearance, urinary output, fractional excretion of sodium, and free water clearance were measured: (a) prior to admission to hospital; (b) during the period from insertion of the urinary catheter until application of the aortic cross-clamp; (c) during the period of aortic cross-clamping; (d) 0-4 h, and (e) 4-8 h after release of the clamp and on days 1, 2, 3, and 5 postoperatively. RESULTS Fenoldopam (0.1 microg kg(-1)min(-1)) administration was not associated with haemodynamic instability. On application of the aortic cross-clamp creatinine clearance decreased significantly in the placebo (83 +/- 20 to 42 +/- 29 mL min(-1) (mean +/- SD)) (P < 0.01) but not in the fenoldopam group, and this decrease persisted for at least 8 h after release of the cross-clamp (83 +/- 20 to 54 +/- 33 mL min(-1) (mean +/- SD)) (P < 0.05). Plasma creatinine concentration increased significantly from baseline on the first postoperative day in the placebo group (87 +/- 12 to 103 +/- 28 micromolL(-1) (mean +/- SD)) (P < 0.01) but not in the fenoldopam group. CONCLUSIONS These findings are consistent with the hypothesis that fenoldopam possesses a renoprotective effect during and after infrarenal aortic cross-clamping.

Fenoldopam: renal and splanchnic effects in patients undergoing coronary artery bypass grafting

Impairment of renal and splanchnic perfusion during and after cardiopulmonary bypass may be responsible for acute renal failure and endotoxin‐mediated systemic inflammation, respectively. We hypothesised that fenoldopam, a selective dopamine receptor agonist, would preserve renal function after cardiopulmonary bypass through its selective renal vasodilatory and natriuretic effects, and increase gastrointestinal mucosal perfusion by selective splanchnic vasodilation. We examined the effects of fenoldopam on haemodynamic parameters, creatinine clearance, fractional excretion of sodium, urine output, free water clearance and gastric mucosal pH in 31 patients undergoing elective coronary revascularisation. Patients were randomly assigned to receive continuous infusions of fenoldopam 0.1 µg.kg−1.min−1 (n = 16) or placebo (n = 15). Renal parameters were measured: during a 24‐h period before hospital admission, during cardiopulmonary bypass, from completion of cardiopulmonary bypass until 4 h later, from 4 to 8 h after cardiopulmonary bypass, and from 8 to 14 h after cardiopulmonary bypass. Gastric intramucosal pH was measured using a gastric tonometer before, during and after cardiopulmonary bypass. In the placebo group, but not the fenoldopam group, mean (SD) creatinine clearance decreased after separation from cardiopulmonary bypass, from 107 (36) to 71 (22) ml.min−1 (p < 0.01) and from 107 (36) to 79 (26) ml.min−1 (p < 0.01) for the 0–4 h and 4–8 h intervals after cardiopulmonary bypass, respectively. Changes in intramucosal pH were similar in both groups. The findings are consistent with the hypothesis that fenoldopam possesses a renoprotective effect in patients undergoing cardiopulmonary bypass.

Nerve growth factor-mediated regulation of pain signalling and proposed new intervention strategies in clinical pain management.

Nerve growth factor (NGF) is the founding member of the neurotrophins family of proteins. It was discovered more than half a century ago through its ability to promote sensory and sympathetic neuronal survival and axonal growth during the development of the peripheral nervous system, and is the paradigmatic target‐derived neurotrophic factor on which the neurotrophic hypothesis is based. Since that time, NGF has also been shown to play a key role in the generation of acute and chronic pain and in hyperalgesia in diverse pain states. NGF is expressed at high levels in damaged or inflamed tissues and facilitates pain transmission by nociceptive neurons through a variety of mechanisms. Genetic mutations in NGF or its tyrosine kinase receptor TrkA, lead to a congenital insensitivity or a decreased ability of humans to perceive pain. The hereditary sensory autonomic neuropathies (HSANs) encompass a spectrum of neuropathies that affect ones ability to perceive sensation. HSAN type IV and HSAN type V are caused by mutations in TrkA and NGF respectively. This review will focus firstly on the biology of NGF and its role in pain modulation. We will review neuropathies and clinical presentations that result from the disruption of NGF signalling in HSAN type IV and HSAN type V and review current advances in developing anti‐NGF therapy for the clinical management of pain.

The associations between severity of early postoperative pain, chronic postsurgical pain and plasma concentration of stable nitric oxide products after breast surgery.

In this study, we compared the effects of two analgesic regimens on perioperative nitric oxide index (NOx) and the likelihood of subsequent development of chronic postsurgical pain (CPSP) after breast surgery and sought to determine the association among early postoperative pain, NOx, and the likelihood of subsequent development of CPSP. Twenty-nine consecutive ASA I or II patients undergoing breast surgery with axillary clearance were randomly allocated to one of two groups. Patients in group S (n = 15) received a standard intraoperative and postoperative analgesic regimen (morphine sulfate, diclofenac, dextropropoxyphene hydrochloride + acetaminophen prn). Patients in group N (n = 14) received a continuous paravertebral block (for 48 h) and acetaminophen and parecoxib (followed by celecoxib up to 5 days). Visual analog scale pain scores at rest and on arm movement were recorded regularly until the fifth postoperative day. A telephone interview was conducted 10 wk postoperatively. The McGill Pain Questionnaire was used to characterize pain. NOx was estimated preoperatively, at the end of surgery, 30 min and 2, 4, 12, 24, 48 h postoperatively. Twelve (80%) patients in group S and no patient in group N developed CPSP (P = 0.009). Compared with patients with a pain rating index ≥1 (n = 18) 10 wk postoperatively, patients with a pain rating index = 0 (n = 11) had lesser visual analog scale pain scores on movement at each postoperative time point from 30 min until 96 h postoperatively (P < 0.005) and at rest 30 min (0.6 ± 1.5 versus 30.2 ± 26.8; P = 0.004), 4 h (2.3 ± 7.5 versus 19.0 ± 25.8; P = 0.013), 8 h (4.4 ± 10.2 versus 21.4 ± 27.0; P = 0.03) and 12 h (0.7 ± 1.2 versus 15.4 ± 27.0; P = 0.035) postoperatively. NOx values were greater in group N compared with group S 48 h postoperatively (40.6 ± 20.1 versus 26.4 ± 13.5; P = 0.04).

Circulating granulocyte macrophage colony-stimulating factor in plasma of patients with the systemic inflammatory response syndrome delays neutrophil apoptosis through inhibition of spontaneous reactive oxygen species generation.

In the normal resolution of an acute inflammatory response apoptosis of neutrophils is essential to maintain immune homeostasis and limit inappropriate host tissue damage by decreasing neutrophil tissue load, function, and release of phlogistic reactive oxygen species and proteases. The systemic inflammatory response syndrome (SIRS), a massive pro-inflammatory immune state, is associated with delayed neutrophil apoptosis, however, the systemic circulating factors and intracellular signal transduction pathways important in regulating neutrophil apoptosis in SIRS are poorly described. Neutrophils isolated from patients with SIRS on admission to the intensive care unit showed significantly (p<.01) delayed spontaneous neutrophil apoptosis compared with healthy neutrophils as quantified using annexin V-FITC and terminal deoxyuridine triphosphate (dUTD) nick end labeling (TUNEL) flow cytometry methods. Plasma from SIRS patients markedly (41.5+/-7.2%, p<.01) inhibited apoptosis of healthy neutrophils compared with controls (69.7+/-4.8%) indicating the presence of soluble circulating factors that can modify the expression of neutrophil apoptosis. Various pro-inflammatory (IL-6, granulocyte macrophage colony-simulating factor, interleukin (IL)-1beta, tumor necrosis factor-alpha) mediators, known to modulate neutrophil apoptosis in vitro, were elevated in the plasma of our cohort of SIRS patients compared with controls. However, the anti-apoptotic effect of SIRS plasma was specifically attenuated (75.5%, p<.01) by neutralizing SIRS plasma of granulocyte macrophage-colony-stimulating factor, but not IL-6, IL-1beta, tumor necrosis factor-alpha. Although the anti-inflammatory cytokine IL-10 was elevated in SIRS plasma (median level 7.2 pg/mL), further boosting SIRS plasma with recombinant human IL-10 (10 ng/mL, levels found in septic shock patients) significantly countered (63.8%, p<.01) the inhibitory effect of SIRS plasma on neutrophil apoptosis. Suppression of neutrophil apoptosis was concomitant with delayed spontaneous elevation of reactive oxygen species, quantified as peroxide production, and reversed by addition of neutralizing antibodies to GM-CSF, and recombinant human IL-10 to SIRS plasma. These results identify circulating GM-CSF as a significant inhibitor of neutrophil apoptosis in patients with SIRS, and that this effect can be countered by boosting SIRS plasma with IL-10. GM-CSF and IL-10 appear to modulate neutrophil apoptosis by altering reactive oxygen species generation in neutrophils.

Thoracic paravertebral block using real-time ultrasound guidance.

BACKGROUND: We developed a technique for ultrasound-guided paravertebral block, which was subsequently applied in the clinical setting. METHODS: An initial cadaver study was used to develop a technique that was used in the clinical setting on patients undergoing breast cancer surgery. RESULTS: Paravertebral catheters were correctly placed in the cadaveric trial in 8 of 10 attempts. In the clinical study, all blocked patients (n = 9) had evidence of thoracic wall sensory block and analgesia postoperatively. CONCLUSIONS: Determined by anatomical dissection, we have described the ultrasound features of the thoracic paravertebral space and performed clinically successful ultrasound-guided paravertebral block.

Airway obstruction following application of cricoid pressure

The widely practiced rapid-sequence induction with application of cricoid pressure is designed to facilitate endotracheal intubation in patients considered to be at high risk of aspiration. We describe a case in which this maneuver was performed on a patient with an undiagnosed traumatic injury to the larynx. The resulting airway obstruction required emergency surgical intervention. The clinical presentation, diagnosis, and management of such injuries are discussed.