Jaap J. de Lange

Impact of Anesthesia Management Characteristics on Severe Morbidity and Mortality

Background: Quantitative estimates of how anesthesia management impacts perioperative morbidity and mortality are limited. The authors performed a study to identify risk factors related to anesthesia management for 24-h postoperative severe morbidity and mortality. Methods: A case-control study was performed of all patients undergoing anesthesia (1995-1997). Cases were patients who either remained comatose or died during or within 24 h of undergoing anesthesia. Controls were patients who neither remained comatose nor died during or within 24 hours of undergoing anesthesia. Data were collected by means of a questionnaire, the anesthesia and recovery form. Odds ratios were calculated for risk factors, adjusted for confounders. Results: The cohort comprised 869,483 patients; 807 cases and 883 controls were analyzed. The incidence of 24-h postoperative death was 8.8 (95% confidence interval, 8.2-9.5) per 10,000 anesthetics. The incidence of coma was 0.5 (95% confidence interval, 0.3-0.6). Anesthesia management factors that were statistically significantly associated with a decreased risk were: equipment check with protocol and checklist (odds ratio, 0.64), documentation of the equipment check (odds ratio, 0.61), a directly available anesthesiologist (odds ratio, 0.46), no change of anesthesiologist during anesthesia (odds ratio, 0.44), presence of a full-time working anesthetic nurse (odds ratio, 0.41), two persons present at emergence (odds ratio, 0.69), reversal of anesthesia (for muscle relaxants and the combination of muscle relaxants and opiates; odds ratios, 0.10 and 0.29, respectively), and postoperative pain medication as opposed to no pain medication, particularly if administered epidurally or intramuscularly as opposed to intravenously. Conclusions: Mortality after surgery is substantial and an association was established between perioperative coma and death and anesthesia management factors like intraoperative presence of anesthesia personnel, administration of drugs intraoperatively and postoperatively, and characteristics of delivered intraoperative and postoperative anesthetic care.

Reactive Oxygen Species Precede Protein Kinase C-δ Activation Independent of Adenosine Triphosphate–sensitive Mitochondrial Channel Opening in Sevoflurane-induced Cardioprotection

BackgroundIn the current study, the authors investigated the distinct role and relative order of protein kinase C (PKC)-&dgr;, adenosine triphosphate–sensitive mitochondrial K+ (mito K+ATP) channels, and reactive oxygen species (ROS) in the signal transduction of sevoflurane-induced cardioprotection and specifically addressed their mechanistic link. MethodsIsolated rat trabeculae were preconditioned with 3.8% sevoflurane and subsequently subjected to an ischemic protocol by superfusion of trabeculae with hypoxic, glucose-free buffer (40 min) followed by 60 min of reperfusion. In addition, the acute affect of sevoflurane on PKC-&dgr; and PKC-&egr; translocation and nitrotyrosine formation was established with use of immunofluorescent analysis. The inhibitors chelerythrine (6 &mgr;m), rottlerin (1 &mgr;m), 5-hydroxydecanoic acid sodium (100 &mgr;m), and n-(2-mercaptopropionyl)-glycine (300 &mgr;m) were used to study the particular role of PKC, PKC-&dgr;, mito K+ATP, and ROS in sevoflurane-related intracellular signaling. ResultsPreconditioning of trabeculae with sevoflurane preserved contractile function after ischemia. This contractile preservation was dependent on PKC-&dgr; activation, mito K+ATP channel opening, and ROS production. In addition, on acute stimulation by sevoflurane, PKC-&dgr; but not PKC-&egr; translocated to the sarcolemmal membrane. This translocation was inhibited by PKC inhibitors and ROS scavenging but not by inhibition of mito K+ATP channels. Furthermore, sevoflurane directly induced nitrosylation of sarcolemmal proteins, suggesting the formation of peroxynitrite. ConclusionsIn sevoflurane-induced cardioprotection, ROS release but not mito K+ATP channel opening precedes PKC-&dgr; activation. Sevoflurane induces sarcolemmal nitrotyrosine formation, which might be involved in the recruitment of PKC-&dgr; to the cell membrane.

Possible nociceptive structures in the sacroiliac joint cartilage: An immunohistochemical study.

The sacroiliac joint (SI joint) is a known source of low back pain. In the absence of validated physical signs and imaging studies, the diagnosis of SI joint pain can be secured by positive response to SI joint intra‐articular infiltration with local anesthetics. The current anatomical and histological knowledge concerning intra‐articular structures of the sacroiliac joint is insufficient to explain the efficacy of this infiltration. Consequently, this study was undertaken to detect the intra‐articular presence of substance P and calcitonin gene‐related peptide (CGRP) positive nerve fibers, providing indirect evidence of nociceptive innervation of the SI joint. Free‐floating sections, obtained from iliac and sacral cartilage and subchondral bone of the SI joint and adjacent ligamentous tissue, of 10 human cadavers were studied immunohistochemically. Tissue of nine human cadavers showed the presence of substance P and CGRP immunoreactivity in the superficial layer of sacral and iliac cartilage, and the surrounding ligamentous structures. Subchondral bone reacted weakly to the antisera used. These findings support the view that the SI joint may be capable of intra‐articular nociception and may explain the positive response to the intra‐articular deposition of local anesthetic. Clin. Anat. 23:192–198, 2010.

Diagnostic criteria for CRPS I: differences between patient profiles using three different diagnostic sets.

Complex Regional Pain Syndrome type I (CRPS I) is an illness which usually occurs due to major or minor tissue injury to the extremities. Because a unique pathophysiological mechanism for CRPS I has not yet been established, the diagnosis is based on observation and measurement of clinical symptoms and signs. In this study, a comparison was made between three sets of diagnostic criteria (the IASP, Bruehl et al. and Veldman et al.) based on patient reports and physicians’ assessments of signs and symptoms associated with CRPS I, in 372 outpatients suspected of having CRPS I. Agreement between CRPS I diagnosis among the three sets was poor (κ‐range: 0.29–0.42), leading to positive CRPS I diagnoses according to Veldman et al.s criteria in 218 cases (59%), according to the IASP in 268 cases (72%), and according to Bruehl et al. in 129 cases (35%). Significant differences in patient profiles were found between the diagnostic sets for the number of patients reporting continuing disproportionate pain, larger area affected than the initial trauma (both p<0.001), increase of symptoms due to exercise (p=0.009), edema (p=0.015), temperature asymmetry (p=0.015), hyperesthesia, allodynia (both p<0.001) and hyperalgesia (p=0.036). Similarly, significant differences emerged for physicians’ observations of hyperesthesia and allodynia (both p<0.001). Highest combined values of sensitivity (SE) and specificity (SP) for the strongest cases of presence (n=108) or absence (n=62) of CRPS I were found for reported hyperesthesia (SE+SP:165%), allodynia (160%), observed color asymmetry (162%), hyperesthesia (157%), temperature asymmetry (154%) and edema (152%). The lack of agreement between the different diagnostic sets for CRPS I and the different clinical profiles that result from it may lead to different therapeutic and study populations, hampering adequate treatment and scientific development for this illness. We propose explicit reference to diagnostic criteria used in studies, and registration in trials of a broad variety of CRPS I features, as used in this study, to make subgroup phenotyping and post hoc analyses based on different diagnostic criteria possible.

The cardioprotective effect of sevoflurane depends on protein kinase C activation, opening of mitochondrial K(+)(ATP) channels, and the production of reactive oxygen species.

Several studies suggest that the cardioprotective effect of sevoflurane depends on protein kinase C (PKC) activation, mitochondrial K+ATP channel (mitoK+ATP) opening, and reactive oxygen species (ROS). However, evidence for their involvement was obtained in separate experimental models. Here, we studied the relative roles of PKC, mitoK+ATP, and ROS in sevoflurane-induced cardioprotection in one model. Rat trabeculae were subjected to simulated ischemia by applying metabolic inhibition (MI) through buffer containing NaCN, followed by 60-min reperfusion. Recovery of active force (Fa) was assessed as percentage of pre-MI force. In time controls, Fa amounted 60% ± 5% at the end of the experiment. The recovery of Fa after MI was reduced to 28% ± 5% (P = 0.045 versus time control), whereas sevoflurane reversed the detrimental effect of MI (Fa recovery, 67% ± 8%; P = 0.01 versus MI). The PKC inhibitor chelerythrine, the mitoK+ATP inhibitor 5-hydroxy decanoic, and the ROS scavenger N-(2-mercaptopropionyl)-glycine all completely abolished the protective effect of sevoflurane (recovery of Fa, 31% ± 8%, 33% ± 8%, and 24% ± 9% for chelerythrine, 5-hydroxy decanoic, and N-(2-mercaptopropionyl)-glycine, respectively). In conclusion, PKC activation, mitoK+ATP channel opening, and ROS production are all essential for sevoflurane-induced cardioprotection. These signaling events are arranged in series within a common signaling pathway, rather than in parallel cascades. Our findings implicate that the perioperative use of sevoflurane preserves cardiac function by preventing ischemia-reperfusion injury.

Cardioprotection Via Activation of Protein Kinase C-δ Depends on Modulation of the Reverse Mode of the Na+/Ca2+ Exchanger

Background— Pretreatment with the volatile anesthetic sevoflurane protects cardiomyocytes against subsequent ischemic episodes caused by a protein kinase C (PKC)-&dgr; mediated preconditioning effect. Sevoflurane directly modulates cardiac Ca2+ handling, and because Ca2+ also serves as a mediator in other cardioprotective signaling pathways, possible involvement of the Na+/Ca2+ exchanger (NCX) in relation with PKC-&dgr; in sevoflurane-induced cardioprotection was investigated. Methods and Results— Isolated right ventricular rat trabeculae were subjected to simulated ischemia and reperfusion (SI/R), consisting of superfusion with hypoxic glucose-free buffer for 40 minutes after rigor development, followed by reperfusion with normoxic glucose containing buffer. Preconditioning with sevoflurane before SI/R improved isometric force development during contractile recovery at 60 minutes after the end of hypoxic superfusion (83±7% [sevo] versus 57±2% [SI/R];n=8; P<0.01). Inhibition of the reverse mode of the NCX by KB-R7943 (10 &mgr;mol/L) or SEA0400 (1 &mgr;mol/L) during preconditioning attenuated the protective effect of sevoflurane. KB-R7943 and SEA0400 did not have intrinsic effects on the contractile recovery. Furthermore, inhibition of the NCX in trabeculae exposed to sevoflurane reduced sevoflurane-induced PKC-&dgr; translocation toward the sarcolemma, as demonstrated by digital imaging fluorescent microscopy. The degree of PKC-&dgr; phosphorylation at serine643 as determined by western blot analysis was not affected by sevoflurane. Conclusions— Sevoflurane-induced cardioprotection depends on the NCX preceding PKC-&dgr; translocation presumably via increased NCX-mediated Ca2+ influx. This may suggest that increased myocardial Ca2+ load triggers the cardioprotective signaling cascade elicited by volatile anesthetic agents similar to other modes of preconditioning.

Central venous catheter placement using the ECG-guided cavafix-certodyn SD catheter

STUDY OBJECTIVE To evaluate the clinical use of a new ECG-guided central venous catheter with regard to positioning in the superior vena cava (SVC). DESIGN Prospective study. SETTING Operating rooms of a university hospital and a general hospital. PATIENTS 89 elective and emergency adult surgical patients requiring central venous catheterization perioperatively. INTERVENTIONS We performed ECG-guided placement of the central venous catheter from several insertion sites. After we observed an intra-atrial p-wave (p-atriale), the catheter was withdrawn 3 cm back into the SVC. Postoperative anterior-posterior chest radiographs were performed for verification of tip localization. MEASUREMENTS AND MAIN RESULTS In all 81 patients who exhibited a p-atriale that reverted to a normal-size p-wave (p-SVC) after withdrawal of the catheter 3 cm, the tip was located in the SVC or the SVC-right atrial junction on the chest radiograph. In 7 of the 8 cases without a p-atriale, the catheter tip was shown to be located at an incorrect position on the chest radiograph. The size of the p-atriale was always at least twice that of the p-SVC. CONCLUSIONS Use of this wire-conducted intravascular ECG signal is a reliable tool for positioning the central venous catheter via various insertion sites. The technique proved to be an inexpensive, easy, and clear method. When a p-atriale is seen, uncomplicated insertions do not require radiologic guidance to control catheter tip position.

Intravenous Magnesium for Complex Regional Pain Syndrome Type 1 (CRPS 1) Patients: A Pilot Study

OBJECTIVES To explore the feasibility of intravenous magnesium administration as a potential candidate intervention for a large size trial in Complex Regional Pain Syndrome Type 1 (CRPS 1). DESIGN Randomized clinical trial. SETTING Outpatient pain clinic. PATIENTS Ten CRPS 1 patients. INTERVENTIONS Eight patients received 70 mg/kg magnesium sulphate infusions in 4 hours for 5 days. For blinding purposes, 2 patients received equal amount NaCl 0.9% solutions (data not analyzed or presented). Interventions were accompanied by standardized physical therapy. OUTCOME MEASURES Pain was assessed using an 11-point Box scale (three times daily for a week) and the McGill Pain Questionnaire. Skin sensitivity was measured with the Semmes Weinstein Monofilaments, (other) impairments with the Impairment Level Sumscore. In addition, functional limitations (Radboud Skills Questionnaire, questionnaire rising and sitting down) and quality of life (Short Form-36 [SF-36], EuroQol) were evaluated. Assessments were performed at baseline, 1, 3, 6, and 12 weeks after intervention. RESULTS Mild systemic side effects were experienced and the infusions were locally well tolerated. Pain was significantly reduced at all follow up compared with baseline (T1: P = 0.01, T3: P = 0.04, T6: P = 0.02, T12: P = 0.02). McGill sensory subscale improved significantly at T1 (number of words chosen: P = 0.03 and pain rating index: P = 0.03). Impairment level (P = 0.03) and quality of life (EuroQol P = 0.04, SF-36 physical P = 0.01) were significantly improved at T12. No improvement was found for skin sensitivity and functional limitations. CONCLUSION Intravenous magnesium significantly improved pain, impairment and quality of life and was well tolerated. The results of this pilot study are encouraging and suggest that magnesium IV as a treatment in CRPS 1 should be further explored in a large size formal trial design.

Continuous brachial plexus block as treatment for the Pancoast syndrome

BACKGROUND Six patients with severe neuropathic pain caused by a Pancoast tumor were treated with the continuous administration of local anesthetics. These patients had not responded to any other treatment, including nonsteroidal anti-inflammatory drugs, opioids, dexamethasone, tricyclic antidepressants, anticonvulsants, ketamine, and transcutaneous electric nerve stimulation. INTERVENTIONS An axillary catheter was placed in the brachial plexus using a posterior approach that has not been described previously. A continuous infusion system of local anesthetics was delivered via a catheter. In two patients, the main purpose was to evaluate the technical possibilities and implications of this new approach. In all patients, the visual analogue scale score was evaluated until the patient died. In four additional patients, the quality of life and performance skills were recorded. RESULTS In all patients, there was a significant reduction in the visual analog scale score, and there was an increase in performance skills and quality of life in four patients. No side effects occurred from this technique or from the continuous administration of local anesthetics. CONCLUSIONS We conclude that neuropathic pain may be treated by local anesthetics administered through an axillary catheter placed in the brachial plexus. This technique is reversible and is preferable to destructive procedures such as cordotomy.

Thoracic sympathectomy: effects on hemodynamics and baroreflex control

Abstract Endoscopic thoracic sympathectomy at T2-T4 is an effective and safe treatment for primary axillary and palmar hyperhidrosis and facial blushing refractory to conventional treatment. T2 and T4 ganglia however are in the direct pathway of sympathetic innervation of the heart and part of the vasomotor nerves. In this study we investigate possible changes in steady-state hemodynamics as well as in beat-to-beat cardiovascular control after thoracoscopic sympathectomy of T2–T4.In 12 patients we measured continuously heart rate (HR) and blood pressure (BP) (non-invasively with Finapres™) during rest and during deep inspiration, in supine and sitting position as well as during a change from lying to standing. Stroke volume (SV) and total peripheral resistance (TPR) were estimated from the BP recordings by the Modelflow method. Markers for cardiovascular control were obtained from power and cross-spectra of BP and HR.After sympathectomy, only in the sitting position was mean HR decreased, while TPR and BP (diastolic and mean) were lower in the supine as well as sitting positions. SV clearly increased. Low frequency power in HR and BP was significantly decreased, just like the max/min ratio in HR after standing up, indicating a diminished capacity in sympathetic vasomotor control. High frequency power of HR as well as baroreflex sensitivity, both parasympathetic markers, did not change in a statistically significant manner.Conclusion: Besides altering steady-state hemodynamics, a thoracic sympathectomy causes relatively small, though measurable changes in cardiovascular control, in particular of peripheral vasomotion.