J.P. Thompson

Endovascular AAA Repair Attenuates the Inflammatory and Renal Responses Associated with Conventional Surgery

PURPOSE To quantify the inflammatory and renal parameters in comparative cohorts of patients undergoing surgical or endovascular repair of abdominal aortic aneurysms (AAAs). METHODS Forty-three patients (41 men; ages 58-81 years) underwent endovascular or conventional aneurysm surgery according to aortic morphology. All patients received a standard general anesthetic and had 12 serial blood and urine samples collected during the perioperative period. Samples underwent analysis for the cytokines interleukin (IL) 1beta tumor necrosis factor-alpha (TNF-alpha), and IL-6. White cell and platelet activation were estimated indirectly by measuring sL-selectin and 11-dehydrothromboxane B2, respectively. The urinary albumin:creatinine ratio (ACR) and N-acetyl-beta-D-glucosaminidase (NAG) activity were estimated to assess renal injury. Fibrinogen and fibrinogen degradation products were calculated to assess activation of the clotting cascade. RESULTS Twenty-three patients underwent endovascular AAA repair and 20 had conventional surgery. Concentrations of IL-6 (p < 0.002) and TNF-alpha (p < 0.0004) were significantly higher in the conventional group. The ACR (p < 0.002) and urinary NAGs (p < 0.0009) were also significantly higher in this group, suggesting greater renal injury. Platelet activity was significantly greater in the endovascular group (p < 0.01), perhaps indicating thrombus organization within the aneurysm sac. CONCLUSIONS These data suggest that the inflammatory response associated with conventional aneurysm repair is largely obviated by endovascular techniques. This may potentially translate to a lower incidence of multiple organ failure after endovascular surgery.

Opioids and immune modulation: more questions than answers

Opioid addicts are more likely to present with infections suggesting opioids are immune modulators. The potential sites/mechanism(s) for this modulation are controversial and on close inspection not well supported by the current literature. It has long been assumed that opioid-induced immune modulation occurs via a combination of direct actions on the immune cell itself, via the hypothalamic-pituitary-adrenal (HPA) axis, or both. Opioid receptors are classified as MOP (μ, mu), DOP (δ, delta), and KOP (κ, kappa)--classical naloxone sensitive receptors--or NOP (the receptor for nociceptin/orphanin FQ), which is naloxone insensitive. Opioids currently used in clinical practice predominantly target the MOP receptor. There do not appear to be classical opioid receptors present on immune cells. The evidence for HPA activation is also poor and shows some species dependence. Most opioids used clinically or as drugs of abuse do not target the NOP receptor. Other possible target sites for immune modulation include the sympathetic nervous system and central sites. We are currently unable to accurately define the cellular target for immune modulation and suggest further investigation is required. Based on the differences observed when comparing studies in laboratory animals and those performed in humans we suggest that further studies in the clinical setting are needed.

Arterial pressure management and carotid endarterectomy

Acute perioperative changes in arterial pressure occur frequently, particularly in patients with cardiovascular disease or those receiving vasoactive medications, or in relation to certain cardiovascular surgical procedures. Both hypo- and hypertension are common in patients undergoing carotid surgery because of unique patho-physiological and surgical factors. Poor arterial pressure control is associated with increased morbidity and mortality after carotid endarterectomy, but good control of arterial pressure is often difficult to achieve in practice. New guidelines have emphasized the benefits of performing carotid surgery urgently in patients with acute neurological symptoms. This strategy may make perioperative arterial pressure control more challenging. However, few specific data are available to guide individual drug therapy. The incidence, implications, and aetiology of haemodynamic instability associated with carotid surgery are reviewed, and some recommendations made for its management. Close monitoring and titration of therapy are probably the most important considerations rather than specific choice of agents.

Analgesia for circumcision in a paediatric population: Comparison of caudal bupivacaine alone with bupivacaine plus two doses of clonidine

Background: Clonidine is often used to improve the duration and quality of analgesia produced by caudal epidural blockade, although the optimum dose of clonidine with bupivacaine remains uncertain.

A comparison of cerebrospinal fluid and plasma urotensin II concentrations in normotensive and hypertensive patients undergoing urological surgery during spinal anesthesia: a pilot study.

Urotensin II is a novel endogenous vasoconstrictor. There are no data describing cerebrospinal fluid (CSF) concentrations in humans. Therefore, in this study, we aimed to quantify and compare plasma and CSF urotensin II concentrations in patients with essential hypertension and matched controls. Twenty male patients (10 receiving >6 mo of treatment for essential hypertension and 10 normotensive controls scheduled to undergo urological surgery under spinal anesthesia) were recruited into this single-blinded cohort study. Plasma and CSF urotensin II concentrations were measured by radioimmunoassay, along with mean arterial blood pressure (MAP), before admission, on the day of admission, and immediately before anesthesia. CSF and plasma urotensin II concentrations were low. Median (range) values in CSF for all 20 patients were significantly lower than plasma by ∼15% (19.0 pg/mL [10.6–24.9 pg/mL] compared with 22.3 pg/mL [17.7–28.4 pg/mL]; P = 0.004). There were no significant differences between normotensive and hypertensive patients in either CSF or plasma concentrations. However, there was a significant positive correlation between average MAP and CSF urotensin II concentrations (r2 = 0.44; P = 0.036) in the hypertensive group.

Nociceptin and urotensin-II concentrations in critically ill patients with sepsis†

BACKGROUND The systemic inflammatory response to infection (sepsis) involves widespread organ dysfunction, including changes in immune modulation, cardiovascular derangements, and neural activation. Two neuropeptide/receptor systems, nociceptin/orphanin FQ (N/OFQ) which acts at the non-classical opioid receptor NOP and urotensin-II (U-II) which acts at the urotensin receptor (UT), have been implicated in neural, immune, and cardiovascular system function. In this study, we make measurements of these peptides in critically ill patients. METHODS Plasma samples from 21 critically ill patients with sepsis were collected over four consecutive days. Plasma N/OFQ and U-II concentrations were determined by radioimmunoassay and compared with biochemical and clinical markers of illness severity, including serum creatinine, bilirubin, platelet and white cell counts, admission APACHE II and serial SOFA scores. RESULTS Median (inter-quartile range) admission plasma N/OFQ concentrations in sepsis were higher in patients who died within 30 days (n=4) compared with survivors (n=17); 3.0 (2.5-5.0) vs 1.0 (1.0-2.5) pg ml(-1) (P=0.028). Plasma N/OFQ concentrations were increased in a subgroup of five patients who had undergone major gastrointestinal surgery. There were no significant changes in plasma U-II concentrations. There were no correlations between plasma U-II and N/OFQ concentrations and markers of illness severity and organ system dysfunction. CONCLUSIONS Plasma N/OFQ concentrations were increased in critically ill patients with sepsis who had undergone major gastrointestinal surgery and in patients who subsequently died. Further work is required to clarify the significance of plasma N/OFQ concentrations in sepsis.

Improved Respiratory Function and Analgesia Control after Endovascular AAA Repair

Purpose: Endovascular abdominal aortic aneurysm (AAA) repair has been proposed as a minimally invasive alternative to conventional surgery and may offer significant advantages in respiratory function and analgesic requirements due to the absence of an abdominal incision. Methods: Respiratory function and analgesic requirements were quantified in 22 age-matched patients undergoing aneurysm repair under general anesthesia. Twelve patients underwent endovascular aneurysm repair, while 10 AAA patients had conventional surgery. One endovascular patient required conversion to conventional repair. Results: The endovascular group required postoperative artificial ventilation for a shorter time (6 versus 21 hours, p < 0.05) and had lower PCA (patient-controlled analgesia) morphine consumption (41 versus 133 mg, p < 0.05) than the conventional group. The endovascular group also had significantly better forced expiratory volume and forced vital capacity at both 3 and 5 days when expressed as percentages of the preoperative values (p < 0.05). Conclusions: Endovascular AAA repair attenuates respiratory dysfunction associated with conventional surgery and reduces perioperative analgesia requirements.

Nociceptin and urotensin-II concentrations in critically ill patients with sepsis.

BACKGROUND The systemic inflammatory response to infection (sepsis) involves widespread organ dysfunction, including changes in immune modulation, cardiovascular derangements, and neural activation. Two neuropeptide/receptor systems, nociceptin/orphanin FQ (N/OFQ) which acts at the non-classical opioid receptor NOP and urotensin-II (U-II) which acts at the urotensin receptor (UT), have been implicated in neural, immune, and cardiovascular system function. In this study, we make measurements of these peptides in critically ill patients. METHODS Plasma samples from 21 critically ill patients with sepsis were collected over four consecutive days. Plasma N/OFQ and U-II concentrations were determined by radioimmunoassay and compared with biochemical and clinical markers of illness severity, including serum creatinine, bilirubin, platelet and white cell counts, admission APACHE II and serial SOFA scores. RESULTS Median (inter-quartile range) admission plasma N/OFQ concentrations in sepsis were higher in patients who died within 30 days (n=4) compared with survivors (n=17); 3.0 (2.5-5.0) vs 1.0 (1.0-2.5) pg ml(-1) (P=0.028). Plasma N/OFQ concentrations were increased in a subgroup of five patients who had undergone major gastrointestinal surgery. There were no significant changes in plasma U-II concentrations. There were no correlations between plasma U-II and N/OFQ concentrations and markers of illness severity and organ system dysfunction. CONCLUSIONS Plasma N/OFQ concentrations were increased in critically ill patients with sepsis who had undergone major gastrointestinal surgery and in patients who subsequently died. Further work is required to clarify the significance of plasma N/OFQ concentrations in sepsis.

Human peripheral blood mononuclear cells express nociceptin/orphanin FQ, but not mu, delta, or kappa opioid receptors.

BACKGROUND:Expression of opioid receptors on peripheral blood mononuclear cells (PBMC) is controversial. These receptors are currently classified as classical (MOP/mu/&mgr;, DOP/delta/&dgr; and KOP/kappa/&kgr;) and nonclassical NOP (nociceptin/orphanin FQ; N/OFQ). METHODS:In this volunteer study we probed for the expression of both classical and nonclassical opioid receptors using 1) radioligand binding, 2) specific antibody binding, and 3) polymerase chain reaction-based experimental paradigms. RESULTS:Membranes prepared from PBMC from healthy volunteers did not bind either [3H]diprenorphine (a nonselective radioligand for classical opioid receptors) or [3H]N/OFQ. There was significant concentration-dependent binding of each radioligand to control tissues expressing recombinant MOP and NOP. In addition, using fluorescence-activated cell sorting paradigms, there was no binding of fluorescent naloxone or either of two MOP antibodies to whole PBMC, though fluorescent naloxone did bind to recombinant MOP (as a positive control). Using primers specific for classical and nonclassical opioid receptors, and RNA extracted from the PBMC of 10 healthy volunteers, we were also unable to detect MOP, DOP, and KOP transcripts. In contrast, NOP was detected in all samples. CONCLUSIONS:Despite using several complementary experimental strategies, we failed to demonstrate protein for classical or nonclassical opioid receptors on PBMC from healthy volunteers. We detected NOP mRNA, suggesting low-density NOP expression on these immunocytes. It is possible that N/OFQ, produced by the PBMC itself, may be involved in the control of immune function.

Comparison of external jugular and central venous pressures in mechanically ventilated patients

Summary We compared central venous pressures, measured via a 150 mm triple lumen catheter in the internal jugular vein with simultaneous external jugular venous pressures, measured with a 5 mm cannula in the external jugular vein, in 24 patients undergoing major surgery. Patients were mechanically ventilated in the supine position. Six sets of paired measurements of mean central venous pressure and mean external jugular venous pressure were taken by a blinded observer, in random order and at end‐expiration at 30‐min intervals during surgery. Four patients were not studied because of a failure to cannulate the external jugular vein. The remaining 20 patients yielded 111 sets of paired measurements. The mean difference between external jugular venous pressure and central venous pressure was 0.3 mmHg over a range of central venous pressure of 0–22 mmHg. Limits of agreement were −3.6 to +3.0 mmHg (95% CI −4.1 to +3.5 mmHg). We conclude that external jugular venous pressure is an accurate estimate of central venous pressure in surgical patients undergoing mechanical ventilation.