Dominic C. Harmon

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.

Aprotinin decreases the incidence of cognitive deficit following CABG and cardiopulmonary bypass: A pilot randomized controlled study

PurposeCognitive deficit after coronary artery bypass surgery (CABG) has a high prevalence and is persistent. Meta-analysis of clinical trials demonstrates a decreased incidence of stroke after CABG when aprotinin is administrated perioperatively. We hypothesized that aprotinin administration would decrease the incidence of cognitive deficit after CABG.MethodsThirty-six ASA III–IV patients undergoing elective CABG were included in a prospective, randomized, single-blinded pilot study. Eighteen patients received aprotinin 2 × 106 KIU (loading dose), 2 × 106 KIU (added to circuit prime) and a continuous infusion of 5 × 105 KIU·hr−1. A battery of cognitive tests was administered to patients and spouses (n = 18) the day before surgery, four days and six weeks postoperatively.ResultsFour days postoperatively new cognitive deficit (defined by a change in one or more cognitive domains using the Reliable Change Index method) was present in ten (58%) patients in the aprotinin group compared to 17 (94%) in the placebo group [95% confidence interval (CI) 0.10–0.62,P = 0.005); (P = 0.01)]. Six weeks postoperatively, four (23%) patients in the aprotinin group had cognitive deficit compared to ten (55%) in the placebo group (95% CI 0.80−0.16,P = 0.005); (P = 0.05).ConclusionIn this prospective pilot study, the incidence of cognitive deficit after CABG and cardiopulmonary bypass is decreased by the administration of high-dose aprotinin.RésuméObjectifLe déficit cognitif qui survient après un pontage aortocoronarien (PAC) persiste seion une forte prévalence. Une méta-analyse d’essais cliniques démontre une incidence réduite d’accident vasculaire cérébral après un PAC quand l’aprotinine périopératoire est administrée. Nous avons émis l’hypothèse que l’aprotinine réduirait l’incidence de déficit cognitif après un PAC.MéthodeTrente-six patients, d’état physique III–IV selon l’ASA, devant subir un PAC réglé, ont été inclus à l’étude pilote, prospective, randomisée et à simple insu. Dix-huit patients ont reçu 2 × 106 UIK d’aprotinine (dose de charge), 2 × 106 UIK (ajouté au circuit d’amorce) et une perfusion continue de 5 × 105 UIK·h−1. Une batterie de tests cognitifs a été administrée aux patients et à leurs conjoints (n = 18) le jour précédant l’opération, quatre jours et six semaines après l’opération.RésultatsQuatre jours après l’opération, un nouveau déficit cognitif (défini par une modification dans au moins un domaine de connaissances selon la méthode de l’index fiable de changement) était présent chez dix (58 %) patients ayant eu de l’aprotinine, comparativement à 17 (94 %) du groupe placebo [intervalle de confiance de 95 % (IC) 0, 10–0,62, P = 0,005) ; (P = 0,01)]. Six semaines après l’opération, quatre (23 %) patients du groupe aprotinine présentaient un déficit cognitif comparativement à dix (55 %) du groupe placebo (IC de 95 % 0,80−0, 16,P = 0,005) ; (P= 0,05).ConclusionL’étude pilote prospective montre que l’incidence de déficit cognitif après un PAC et une circulation extracorporelle est réduite par l’administration d’aprotinine à doses élevées.

The effect of lidocaine on in vitro neutrophil and endothelial adhesion molecule expression induced by plasma obtained during tourniquet-induced ischaemia and reperfusion.

Background: Changes in neutrophil and endothelial adhesion molecule expression occur during perioperative ischaemia and reperfusion (I/R) injury. We investigated the effects of lidocaine on neutrophil-independent changes in neutrophil and endothelial adhesion molecule expression associated with tourniquet-induced I/R. Methods: Plasma was obtained from venous blood samples (tourniquet arm) taken before (baseline), during, 15 min, 2 and 24h following tourniquet release in seven patients undergoing elective upper limb surgery with tourniquet application. Isolated neutrophils from healthy volunteers (n = 7) were pretreated in the presence or absence of lidocaine (0.005, 0.05 and 0.5 mg mL−1) for 1 h, and then incubated with I/R plasma for 2 h. Human umbilical vein endothelial cells (HUVECs) were pretreated in the presence or absence of lidocaine (0.005, 0.05 and 0.5 mg mL−1) for 1 h, and then incubated with the plasma for 4 h. Adhesion molecule expression was estimated using flow cytometry. Data were analysed using ANOVA and post hoc Student-Newman-Keuls tests. Results: I/R plasma (withdrawn 15 min following tourniquet release) increased isolated neutrophil CD11b (P = 0.03), CD18 (P = 0.01) and endothelial intercellular adhesion molecule-1 (ICAM-1) (P = 0.008) expression compared to baseline. CD11b, CD18 and ICAM-1 expression on lidocaine (0.005 mg mL−1) treated neutrophils was similar to control. CD11b (P < 0.001), CD18 (P = 0.03) and ICAM-1 (P = 0.002) expression on lidocaine (0.05 mg mL−1) treated neutrophils and HUVECs was less than that on controls. Conclusion: Increased in vitro neutrophil and endothelial cell adhesion molecule expression on exposure to plasma obtained during the early reperfusion phase is diminished by lidocaine at greater than clinically relevant plasma concentrations.

Activated endothelial interleukin-1beta, -6, and -8 concentrations and intercellular adhesion molecule-1 expression are attenuated by lidocaine.

Endothelial cells play a key role in ischemia reperfusion injury. We investigated the effects of lidocaine on activated human umbilical vein endothelial cell (HUVEC) interleukin (IL)-1&bgr;, IL-6, and IL-8 concentrations and intercellular adhesion molecule-1 (ICAM-1) expression. HUVECs were pretreated with different concentrations of lidocaine (0 to 0.5 mg/mL) for 60 min, thereafter tumor necrosis factor-&agr; was added at a concentration of 2.5 ng/mL and the cells incubated for 4 h. Supernatants were harvested, and cytokine concentrations were analyzed by enzyme-linked immunosorbent assay. Endothelial ICAM-1 expression was analyzed by using flow cytometry. Differences were assessed using analysis of variance and post hoc unpaired Student’s t-test where appropriate. Lidocaine (0.5 mg/mL) decreased IL-1&bgr; (1.89 ± 0.11 versus 4.16 ± 1.27 pg/mL; P = 0.009), IL-6 (65.5 ± 5.14 versus 162 ± 11.5 pg/mL; P < 0.001), and IL-8 (3869 ± 785 versus 14,961 ± 406 pg/mL; P < 0.001) concentrations compared with the control. IL-1&bgr;, IL-6, and IL-8 concentrations in HUVECs treated with clinically relevant plasma concentrations of lidocaine (0.005 mg/mL) were similar to control. ICAM-1 expression on lidocaine-treated (0.05 mg/mL) HUVECs was less than on controls (198 ± 52.7 versus 298 ± 50.3; Mean Channel Fluorescence; P < 0.001). Activated endothelial IL-1&bgr;, IL-6, and IL-8 concentrations and ICAM-1 expression are attenuated only by lidocaine at concentrations larger than clinically relevant concentrations.

The effect of lidocaine on neutrophil CD11b/CD18 and endothelial ICAM-1 expression and IL-1β concentrations induced by hypoxia–reoxygenation

Background: Lidocaine has actions potentially of benefit during ischaemia-reperfusion. Neutrophils and endothelial cells have an important role in ischaemia-reperfusion injury. Methods: Isolated human neutrophil CD11b and CD18, and human umbilical vein endothelial cell (HUVEC) ICAM-1 expression and supernatant IL-1β concentrations in response to hypoxia-reoxygenation were studied in the presence or absence of different concentrations of lidocaine (0.005, 0.05 and 0.5 mg mL−1). Adhesion molecule expression was quantified by flow cytometry and IL-1β concentrations by ELISA. Differences were assessed with analysis of variance and Student-Newman-Keuls as appropriate. Data are presented as mean ± SD. Results: Exposure to hypoxia-reoxygenation increased neutrophil CD11b (94.33 ± 40.65 vs. 34.32 ± 6.83 mean channel fluorescence (MCF), P = 0.02), CD18 (109.84 ± 35.44 vs. 59.05 ± 6.71 MCF, P = 0.03) and endothelial ICAM-1 (146.62 ± 16.78 vs. 47.29 ± 9.85 MCF, P < 0.001) expression compared to normoxia. Neutrophil CD18 expression on exposure to hypoxia-reoxygenation was less in lidocaine (0.005 mg mL−1) treated cells compared to control (71.07 ± 10.14 vs. 109.84 ± 35.44 MCF, P = 0.03). Endothelial ICAM-1 expression on exposure to hypoxia-reoxygenation was less in lidocaine (0.005 mg mL−1) treated cells compared to control (133.25 ± 16.05 vs. 146.62 ± 16.78 MCF, P = 0.03). Hypoxia-reoxygenation increased HUVEC supernatant IL-1β concentrations compared to normoxia (3.41 ± 0.36 vs. 2.65 ± 0.21 pg mL−1, P = 0.02). Endothelial supernatant IL-1β concentrations in lidocaine-treated HUVECs were similar to controls. Conclusions: Lidocaine at clinically relevant concentrations decreased neutrophil CD18 and endothelial ICAM-1 expression but not endothelial IL-1β concentrations.

The effect of aprotinin on hypoxia-reoxygenation-induced changes in neutrophil and endothelial function.

Background and objective: An acute inflammatory response associated with cerebral ischaemia-reperfusion contributes to the development of brain injury. Aprotinin has potential, though unexplained, neuroprotective effects in patients undergoing cardiac surgery. Methods: Human neutrophil CD11b/CD18, endothelial cell intercellular adhesion molecule-1 (ICAM-1) expression and endothelial interleukin (IL)-1β supernatant concentrations in response to in vitro hypoxia-reoxygenation was studied in the presence or absence of aprotinin (1600 KIU mL−1). Adhesion molecule expression was quantified using flow cytometry and IL-1β concentrations by enzyme-linked immunosorbent assay. Data were analysed using ANOVA and post hoc Student-Newman-Keuls test as appropriate. Results: Exposure to 60-min hypoxia increased neutrophil CD11b expression compared to normoxia (170 ± 46% vs. 91 ± 27%, P = 0.001) (percent intensity of fluorescence compared to time 0) (n = 8). Hypoxia (60 min) produced greater upregulation of CD11b expression in controls compared to aprotinin-treated neutrophils [(170 ± 46% vs. 129 ± 40%) (P = 0.04)] (n = 8). Hypoxia-reoxygenation increased endothelial cell ICAM-1 expression (155 ± 3.7 vs. 43 ± 21 mean channel fluorescence, P = 0.0003) and IL-1β supernatant concentrations compared to normoxia (3.4 ± 0.4 vs. 2.6 ± 0.2, P = 0.02) (n = 3). Hypoxia-reoxygenation produced greater upregulation of ICAM-1 expression [(155 ± 3.3 vs. 116 ± 0.7) (P = 0.001)] and IL-1β supernatant concentrations [(3.4 ± 0.3 vs. 2.6 ± 0.1) (P = 0.01)] in controls compared to aprotinin-treated endothelial cell preparation (n = 3). Conclusions: Hypoxia-reoxygenation-induced upregulation of neutrophil CD11b, endothelial cell ICAM-1 expression and IL-1β concentrations is decreased by aprotinin at clinically relevant concentrations.

A combination of lidocaine and nitrous oxide in oxygen is more effective in preventing pain on propofol injection than either treatment alone

Background and objective: Propofol is an intravenous (i.v.) anaesthetic agent that possesses many of the qualities of an ideal anaesthetic agent. The most significant side‐effect associated with propofol is pain on injection. Despite optimal therapy, the incidence of pain on propofol injection remains a problem. This prospective, randomized, double blinded study evaluated the effect of three different treatment strategies in decreasing pain on propofol injection. Methods: We studied 102 adult, ASA I‐II patients, scheduled for elective surgical procedures. Combination of i.v. lidocaine and nitrous oxide (N2O) in oxygen (O2) inhalation pre‐treatment was compared with either treatment alone in the prevention of pain on propofol injection. A standard propofol injection technique and scoring system, to measure the pain on injection was used. Results: Demographic variables were similar between the groups. The incidence of no pain on propofol injection was similar in the lidocaine and N2O groups (63.6% vs. 57.5%) (95% confidence interval (CI): 0.17‐0.29, P = 0.61). Combination therapy was associated with a greater incidence of no pain on injection (84% vs. 63.6%) (95% CI: 0.06‐0.48, P = 0.04). Conclusion: Combination of i.v. lidocaine and N2O in O2 inhalation pre‐treatment is more effective than either treatment alone in decreasing pain on propofol injection.

Effect of midazolam on in vitro cerebral endothelial ICAM-1 expression induced by astrocyte-conditioned medium

Background and objective: Astrocytes exposed to hypoxia produce pro‐inflammatory cytokines and upregulate intercellular adhesion molecule‐1 on cerebral endothelium. This study investigated the effects of midazolam on this response. Methods: Mouse astrocytes were exposed to 4 h of hypoxia and 24 h of reoxygenation. Astrocyte‐conditioned medium were applied to mouse cerebral endothelial cell cultures for 4 h and 24 h in normoxia. Endothelial cells were pre‐incubated for 1 h with midazolam (0, 5, 50 μg L−1). Flow cytometry was used to estimate endothelial ICAM‐1 expression. IL‐1β concentrations were measured with ELISA. Repeated comparisons were made using ANOVA and post hoc Tukey Test as appropriate. Data are mean (SD). Results: Mouse cerebral endothelial cell ICAM‐1 expression was greater after 24 h exposure to hypoxia–reoxygenation astrocyte‐conditioned medium compared to normoxic astrocyte‐conditioned medium (mean channel flouresence 112.5 (9.5) vs. 81.5 (7.5), P = 0.01). ICAM‐1 expression was decreased by midazolam (5 μg L−1) compared to control (mean channel flouresence 81.35 (7.5) vs. 112.5 (9.5), P = 0.01). Supernatant IL‐1β concentrations (pg mL−1) in astrocytes exposed to hypoxia–reoxygenation were greater than those exposed to normoxia (16.41 (2.35) vs. 10.5 (2.13), P = 0.01). Conclusion: We conclude that decreased cerebral endothelial ICAM‐1 expression in response to activated glial cell compartment by midazolam may decrease post ischaemic brain inflammation and secondary brain injury.

The use of ultrasound-guided hematoma blocks in wrist fractures

determined clinical data has been shown [2,3], and is again confirmed by this study. By undertaking an appropriate simulation, the authors might have developed their clinical sequence using fewer resources, but it is still important to confirm the simulation by empirical research. In addition, if a clinician wishes to aim for a different FA endpoint from that chosen by the authors, then it is not necessary to repeat the entire study; all that is required is that different parameters be tested until an adequate sequence is determined. Finally, the simulation reaffirms that there is a lag between FA and the effector site concentration, shown as the Vessel Rich Group, which includes the brain and spinal cord and is represented by the trace labeled R.

An anatomical study of the parasacral block using magnetic resonance imaging of healthy volunteers.

BACKGROUND: The parasacral approach to sciatic blockade is reported to be easy to learn and perform, with a high success rate and few complications. METHODS: Using magnetic resonance imaging, we evaluated the accuracy of a simulated needle (perpendicular to skin) in contacting the sacral plexus with this approach in 10 volunteers. Intrapelvic structures encountered during the simulated parasacral blocks were also recorded. RESULTS: The sacral plexus was contacted by the simulated needle in 4 of the 10 volunteers, and the sciatic nerve itself in one volunteer. The plexus was accurately located adjacent to a variety of visceral structures, including small bowel, blood vessels, and ovary. In the remaining five volunteers (in whom the plexus was not contacted on first needle pass), small bowel, rectum, blood vessels, seminal vesicles, and bony structures were encountered. Historically, when plexus is not encountered, readjustment of the needle insertion point more caudally has been recommended. We found that such an adjustment resulted in simulated perforation of intrapelvic organs or the perianal fossa. CONCLUSIONS: These findings question the reliability of the anatomical landmarks of the parasacral block and raise the possibility of frequent visceral puncture using this technique.