Observer Variability as a Determinant of Measurement Error of Ultrasonographic Measurements of the Optic Nerve Sheath Diameter: A Systematic Review.

BACKGROUND: Ultrasonographic measurements of the diameter of the sheath of the optic nerve can be used to assess intracranial pressure indirectly. These measurements come with measurement error. OBJECTIVE: Our aim was to estimate observer's measurement error as a determinant of ultrasonographic measurement variability of the optic nerve sheath diameter. METHODS: A systematic search of the literature was conducted in Embase, Medline, Web of Science, the Cochrane Central Register of Trials, and the first 200 articles of Google Scholar up to April 19, 2021. Inclusion criteria were the following: healthy adults, B-mode ultrasonography, and measurements 3 mm behind the retina. Studies were excluded if standard error of measurement could not be calculated. Nine studies featuring 389 participants (median 40; range 15-100) and 22 observers (median 2; range 1-4) were included. Standard error of measurement and minimal detectable differences were calculated to quantify observer variability. Quality and risk of bias were assessed with the Guidelines for Reporting Reliability and Agreement Studies. RESULTS: The standard error of measurement of the intra- and interobserver variability had a range of 0.10-0.41 mm and 0.14-0.42 mm, respectively. Minimal detectable difference of a single observer was 0.28-1.1 mm. Minimal detectable difference of multiple observers (range 2-4) was 0.40-1.1 mm. Quality assessment showed room for methodological improvement of included studies. CONCLUSIONS: The standard errors of measurement and minimal detectable differences of ultrasonographic measurements of the optic nerve sheath diameter found in this review with healthy participants indicate caution should be urged when interpreting results acquired with this measurement method in clinical context.

Intrathecal hydrophilic opioids for abdominal surgery: a meta-analysis, meta-regression, and trial sequential analysis.

BACKGROUND: Intrathecal hydrophilic opioids decrease systemic opioid consumption after abdominal surgery and potentially facilitate enhanced recovery. A meta-analysis is needed to quantify associated risks and benefits. METHODS: A systematic search was performed to find RCTs investigating intrathecal hydrophilic opioids in abdominal surgery. Caesarean section and continuous regional or neuraxial techniques were excluded. Several subgroup analyses were prespecified. A conventional meta-analysis, meta-regression, trial sequential analysis, and provision of GRADE scores were planned. RESULTS: The search yielded 40 trials consisting of 2500 patients. A difference was detected in 'i.v. morphine consumption' at Day 1 {mean difference [MD] -18.4 mg, (95% confidence interval [CI]: -22.3 to -14.4)} and Day 2 (MD -25.5 mg [95% CI: -30.2 to -20.8]), pain scores at Day 1 in rest (MD -0.9 [95% CI: -1.1 to -0.7]) and during movement (MD -1.2 [95% CI: -1.6 to -0.8]), length of stay (MD -0.2 days [95% CI: -0.4 to -0.1]) and pruritus (relative risk 4.3 [95% CI: 2.5-7.5]) but not in nausea or sedation. A difference was detected for respiratory depression (odds ratio 5.5 [95% CI: 2.1-14.2]) but not when two small outlying studies were excluded (odds ratio 1.4 [95% CI: 0.4-5.2]). The level of evidence was graded as high for morphine consumption, in part because the required information size was reached. CONCLUSIONS: This study showed important opioid-sparing effects of intrathecal hydrophilic opioids. Our data suggest a dose-dependent relationship between the risk of respiratory depression and the dose of intrathecal opioids. Excluding two high-dose studies, intrathecal opioids have a comparable incidence of respiratory depression as the control group. CLINICAL TRIAL REGISTRATION: PROSPERO-registry: CRD42018090682.

Recovery of cefazolin and clindamycin in in vitro pediatric CPB systems.

Cardiopulmonary bypass (CPB) is often necessary for congenital cardiac surgery, but CPB can alter drug pharmacokinetic parameters resulting in underdosing. Inadequate plasma levels of antibiotics could lead to postoperative infections with increased morbidity. The influence of pediatric CPB systems on cefazolin and clindamycin plasma levels is not known. We have measured plasma levels of cefazolin and clindamycin in in vitro pediatric CPB systems. We have tested three types of CPB systems. All systems were primed and spiked with clindamycin and cefazolin. Samples were taken at different time points to measure the recovery of cefazolin and clindamycin. Linear mixed model analyses were performed to assess if drug recovery was different between the type of CPB system and sampling time point. The experiments were conducted at a tertiary university hospital. 81 samples were analyzed. There was a significant difference in the recovery over time between CPB systems for cefazolin and clindamycin (P < .001). Cefazolin recovery after 180 minutes was 106% (95% CI: 91-123) for neonatal, 99% (95% CI: 85-115) for infant, and 77% (95% CI: 67-89) for pediatric systems. Clindamycin recovery after 180 minutes was 143% (95% CI: 116-177) for neonatal, 111% (95% CI: 89-137) for infant, and 120% (95% CI: 97-149) for pediatric systems. Clindamycin recovery after 180 minutes compared to the theoretical concentration was 0.4% for neonatal, 1.2% for infants, and 0.6% for pediatric systems. The recovery of cefazolin was high in the neonatal and infant CPB systems and moderate in the pediatric system. We found a large discrepancy between the theoretical and measured concentrations of clindamycin in all tested CPB systems.

The effect of midazolam as premedication on the quality of postoperative recovery after laparotomy: a randomized clinical trial.

PURPOSE: Despite the uncertain effects of anxiolytic premedication with benzodiazepines on the quality of postoperative recovery, perioperative benzodiazepine administration is still a common practice in many hospitals. We evaluated the effect of premedication with midazolam on the quality of recovery in hospitalized patients undergoing a laparotomy. METHODS: We conducted a single-centre randomized placebo-controlled, double-blinded clinical trial from July 2014 to September 2015. We included 192 patients aged > 18 yr scheduled for elective laparotomy with a planned postoperative stay of ≥ three days. Participants were randomized into two groups to receive either midazolam 3 mg or sodium chloride 0.9% intravenously as premedication prior to surgery. Patients were followed up for up to one week after surgery. The primary outcome was the Quality of Recovery-40 (QoR-40) score on postoperative day (POD) 3. The secondary outcomes included the QoR-40 score on POD 7, and the State-Trait Anxiety Inventory, State-Trait Anger Scale, Multidimensional Fatigue Inventory, and the Hospital Anxiety and Depression Scale scores. RESULTS: The mean (standard deviation) postoperative QoR-40 scores on POD 3 were not significantly different in the midazolam group compared with controls [166.4 (17.0) vs 163.9 (19.8), respectively; mean difference, 2.3; 95% confidence interval, - 2.9 to 8.4; P = 0.35]. There were no between-group differences in any of the secondary outcomes. CONCLUSIONS: Administration of midazolam as premedication for laparotomy patients did not improve the quality of recovery up to one week after surgery. General prescription of midazolam as premedication can be questioned and might only suit some patients. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01993459); registered 29 October, 2013.

In Vitro Recovery of Sufentanil, Midazolam, Propofol, and Methylprednisolone in Pediatric Cardiopulmonary Bypass Systems.

OBJECTIVES: To evaluate in vitro drug recovery in cardiopulmonary bypass (CPB) systems used for pediatric cardiac surgery. DESIGN: Observational in vitro study. SETTING: Single-center university hospital. PARTICIPANTS: In vitro CPB systems used for pediatric cardiac surgery. INTERVENTIONS: Three full neonatal, infant, and pediatric CPB systems were primed according to hospital protocol and kept running for 6 hours. Midazolam, propofol, sufentanil, and methylprednisolone were added to the venous side of the systems in doses commonly used for induction of general anesthesia. Blood samples were taken from the postoxygenator side of the circuit immediately after injection of the drugs and after 2, 5, 7, 10, 30, 60, 180, and 300 minutes. MEASUREMENTS AND MAIN RESULTS: Linear mixed model analyses were performed to assess the relationship between log-transformed drug concentration (dependent variable) and type of CPB system and sample time point (independent variables). The mean percentage of drug recovery after 60 and 180 minutes compared with T1 was 41.7% (95% confidence interval [CI] 35.9-47.4) and 23.0% (95% CI 9.2-36.8) for sufentanil, 87.3% (95% CI 64.9-109.7) and 82.0% (95% CI 64.6-99.4) for midazolam, 41.3% (95% CI 15.5-67.2) and 25.0% (95% CI 4.7-45.3) for propofol, and 119.3% (95% CI 101.89-136.78) and 162.0% (95% CI 114.09-209.91) for methylprednisolone, respectively. CONCLUSIONS: The present in vitro experiment with neonatal, infant, and pediatric CPB systems shows a variable recovery of routinely used drugs with significant differences between drugs, but not between system categories (with the exception of propofol). The decreased recovery of mainly sufentanil and propofol could lead to suboptimal dosing of patients during cardiac surgery with CPB.

Efficiency and efficacy of planning and care on a post-anesthesia care unit: a retrospective cohort study.

BACKGROUND: In the post-anesthesia care unit in our hospital, selected postoperative patients receive care from anesthesiologists and nursing staff if these patients require intensive hemodynamic monitoring or treatment to stabilize vital functions (e.g., vasopressor use and mechanical ventilation support) during a one-night admission. We investigated the agreement between elective preoperative planning for post-anesthesia care unit admission and the postoperative reality, along with the consequences of planning failures. METHODS: Data from records for 479 consecutive patients from June 1 to November 30, 2014, in a tertiary referral hospital were reviewed and analyzed. All patients admitted to PACU were included, along with patients scheduled to be referred to PACU but ultimately transferred to another ward. The primary outcome was the efficiency of planning PACU admission for elective patients. Secondary outcomes included secondary admissions to PACU or the intensive care unit (ICU) and 30-day morbidity and mortality. RESULTS: Of the 479 included patients, 342 (71%) were admitted per preoperative planning. Five patients (1%) needed cardiopulmonary resuscitation, and six (1%) did not survive the follow-up period. Patients admitted to PACU because of a shortage of beds in the ICU had the highest readmission (20%) and mortality rates (20%) (P = 0.01). CONCLUSIONS: Preoperative planning for PACU admission was off-target for 29%. However, efficient care always takes precedence over efficient planning. In particular, downgrading patients to PACU because of a shortage of beds in the ICU was associated with a mortality increase.

Immediate postoperative high-sensitivity troponin T concentrations and long-term patient-reported health-related quality of life: A prospective cohort study.

BACKGROUND: Myocardial injury after noncardiac surgery is associated with mortality and major adverse postoperative cardiovascular events. The effect of postoperative troponin concentrations on patient-reported health-related quality of life (HRQoL) is unknown. OBJECTIVE: The study examined the association between immediate postoperative troponin concentrations and self-reported HRQoL 1 year after surgery. DESIGN: Prospective cohort study. SETTING: Single-centre tertiary care hospital in the Netherlands between July 2012 and 2015. PATIENTS: Patients aged at least 60 years undergoing moderate and major noncardiac surgery. INTERVENTION: None. MAIN OUTCOME MEASURES: HRQoL total score was assessed with the EuroQol five-dimensional questionnaire. Tobit regression analysis was used to determine the association between postoperative troponin concentrations and 1-year HRQoL. Peak high-sensitivity troponin T values were divided into four categories: less than 14, 14 to 49, 50 to 149 and at least 150 ng l. RESULTS: A total of 3085 patients with troponin measurements were included. 2634 (85.4%) patients were alive at 1-year follow-up of whom 1297 (49.2%) returned a completed questionnaire. The median score for HRQoL was 0.82 (0.85, 0.81, 0.77 and 0.71 per increasing troponin category). Multivariable analysis revealed betas of -0.06 [95% confidence interval (CI) -0.09 to -0.02], -0.11 (95% CI -0.18 to -0.04) and -0.18 (95% CI -0.29 to -0.07) for troponin levels of 14 to 49, 50 to 149 and at least 150 ng l when compared with values less than 14 ng l. Other independent predictors for lower HRQoL were chronic obstructive pulmonary disease, female sex, peripheral arterial disease and increasing age. CONCLUSION: Higher levels of postoperative troponin measured immediately after surgery were independently associated with lower self-reported HRQoL total score at 1-year follow-up.

Current state of noninvasive, continuous monitoring modalities in pediatric anesthesiology.

PURPOSE OF REVIEW: The last decades, anesthesia has become safer, partly due to developments in monitoring. Advanced monitoring of children under anesthesia is challenging, due to lack of evidence, validity and size constraints. Most measured parameters are proxies for end organ function, in which an anesthesiologist is actually interested. Ideally, monitoring should be continuous, noninvasive and accurate. This present review summarizes the current literature on noninvasive monitoring in noncardiac pediatric anesthesia. RECENT FINDINGS: For cardiac output (CO) monitoring, bolus thermodilution is still considered the gold standard. New noninvasive techniques based on bioimpedance and pulse contour analysis are promising, but require more refining in accuracy of CO values in children. Near-infrared spectroscopy is most commonly used in cardiac surgery despite there being no consensus on safety margins. Its place in noncardiac anesthesia has yet to be determined. Transcutaneous measurements of blood gases are used mainly in the neonatal intensive care unit, and is finding its way to the pediatric operation theatre. Especially CO2 measurements are accurate and useful. SUMMARY: New techniques are available to assess a child's hemodynamic and respiratory status while under anesthesia. These new monitors can be used as complementary tools together with standard monitoring in children, to further improve perioperative safety.

Risk of abdominal aortic aneurysm (AAA) among male and female relatives of AAA patients.

Sex affects the presentation, treatment, and outcomes of abdominal aortic aneurysm (AAA). Although AAAs are less prevalent in women, at least in the general population, women with an AAA have a poorer prognosis in comparison to men. Sex differences in the genetic predisposition for aneurysm disease remain to be established. In this study we investigated the familial risk of AAA for women compared to men. All living AAA patients included in a 2004-2012 prospective database were invited to the multidisciplinary vascular/genetics outpatient clinic between 2009 and 2012 for assessment of family history using detailed questionnaires. AAA risk for male and female relatives was calculated separately and stratified by sex of the AAA patients. Families of 568 AAA patients were investigated and 22.5% of the patients had at least one affected relative. Female relatives had a 2.8-fold and male relatives had a 1.7-fold higher risk than the estimated sex-specific population risk. Relatives of female AAA patients had a higher aneurysm risk than relatives of male patients (9.0 vs 5.9%, p = 0.022), corresponding to 5.5- and 2.0-fold increases in aneurysm risk in the female and male relatives, respectively. The risk for aortic aneurysm in relatives of AAA patients is higher than expected from population risk. The excess risk is highest for the female relatives of AAA patients and for the relatives of female AAA patients. These findings endorse targeted AAA family screening for female and male relatives of all AAA patients.

Life expectancy and causes of death after repair of intact and ruptured abdominal aortic aneurysms.

BACKGROUND: Life expectancy and causes of death after abdominal aortic aneurysm (AAA) repair are not well characterized. Population aging and improved secondary prevention may have modified the prognosis of these patients. We designed a retrospective cohort study to determine the vital prognosis, causes of death, and differences in outcome after intact and ruptured AAA. METHODS: All patients with AAA treated from 2003 to 2011 at a single university institution in The Netherlands were analyzed. Survival status was derived from civil registry data. Causes of death were obtained from death certificates. The primary end point was overall mortality. Secondary end points were cardiovascular, cancer-related, and AAA-related mortality. Predictors for perioperative and late survival were obtained by logistic regression and Cox regression models, respectively. RESULTS: The study included 619 consecutive AAA patients (12% women; mean age, 72 years), of whom 152 (24.5%) had ruptured AAAs. Endovascular repair was performed in 390 (63%). Rupture (odds ratio [OR], 10.63; 95% confidence interval [CI], 4.80-23.5), open repair (OR, 3.59; 95% CI, 1.69-7.62), renal insufficiency (OR, 2.94; 95% CI, 1.51-3.46), and age (OR, 1.08 per year; 95% CI, 1.09-1.15) were predictors of 30-day mortality. Five-year survival expectancy was 65% for intact AAA and 41% for ruptured AAA (P < .001). Cardiovascular deaths unrelated to the AAA occurred in 35% and cancer-related deaths in 29% of deceased patients. Predictors for late mortality were history of prior malignant disease (hazard ratio, 2.83; 95% CI, 1.99-4.03) and age (hazard ratio, 1.08 per year; 95% CI, 1.05-1.10). After 30 days, only six deaths (1.1%) were AAA related. CONCLUSIONS: Endovascular repair reduced perioperative mortality by threefold, but no survival benefit was observed at long term. After the perioperative period, survival of ruptured AAA and intact AAA patients was not different. Deaths were distributed in similar proportions between cardiovascular and cancer-related causes.

Cutaneous Mitochondrial PO2, but Not Tissue Oxygen Saturation, Is an Early Indicator of the Physiologic Limit of Hemodilution in the Pig.

BACKGROUND: Hemodilution is a consequence of fluid replacement during blood loss and is limited by the individual ability to compensate for decreasing hemoglobin level. We tested the ability of a novel noninvasive method for measuring cutaneous mitochondrial PO2 (mitoPO2) to detect this threshold early. METHODS: Anesthetized and ventilated pigs were hemodynamically monitored and randomized into a hemodilution (n = 12) or a time control (TC) group (n = 14). MitoPO2 measurements were done by oxygen-dependent delayed fluorescence of protoporphyrin IX after preparation of the skin with 20% 5-aminolevulinic acid cream. Tissue oxygen saturation (StO2) was measured with near infrared spectroscopy on the thoracic wall. After baseline measurements, progressive normovolemic hemodilution was performed in the hemodilution group in equal steps (500 ml blood replaced by 500 ml Voluven; Fresenius Kabi AG, Germany). Consecutive measurements were performed after 20-min stabilization periods and repeated 8 times or until the animal died. RESULTS: The TC animals remained stable with regard to hemodynamics and mitoPO2. In the hemodilution group, mitoPO2 became hemoglobin-dependent after reaching a threshold of 2.6 ± 0.2 g/dl. During hemodilution, hemoglobin and mitoPO2 decreased (7.9 ± 0.2 to 2.1 ± 0.2 g/dl; 23.6 ± 2 to 9.9 ± 0.8 mmHg), but StO2 did not. Notably, mitoPO2 dropped quite abruptly (about 39%) at the individual threshold. We observed that this decrease in mitoPO2 occurred at least one hemodilution step before changes in other conventional parameters. CONCLUSIONS: Cutaneous mitoPO2 decreased typically one hemodilution step before occurrence of significant alterations in systemic oxygen consumption and lactate levels. This makes mitoPO2 a potential early indicator of the physiologic limit of hemodilution and possibly a physiologic trigger for blood transfusion.

Pathophysiological Mechanisms Involved in Vasomotor Disturbances in Complex Regional Pain Syndrome and Implications for Therapy: A Review.

Complex regional pain syndrome (CRPS) is characterized by continuous pain, disproportional to the initial trauma. It usually spreads to the distal parts of the affected limb. Besides continuing pain, a mix of sensory, sudo- and vasomotor disturbances, motor dysfunction, and trophic changes is responsible for physical complaints. Vasomotor disturbance is characterized by changes in skin temperature and color. In CRPS patients with a cold extremity, a decrease in blood flow can cause decreased tissue saturation and tissue acidosis, resulting in ischemic pain. The pathophysiology of vasomotor disturbances is not completely understood. Temperature asymmetry is generally assumed as a result of disturbance in the sympathetic nervous system. Vasodilating drugs and sympathetic blockade have been cornerstones of therapy in cold CRPS for years. However, only a limited part of these patients improve on this kind of therapies. Research has shown a pivotal role for inflammation in the pathophysiology of CRPS. Inflammation can result in endothelial dysfunction. Endothelial function plays an important role in the local regulation of vascular tone. Endothelial dysfunction could be another mechanism responsible for the vasomotor disturbances in cold CRPS. An important goal in the treatment of cold-type CRPS is the restoration of a normal blood flow. Consequently it is important to distinguish the underlying pathophysiological mechanisms of vasomotor disturbances. A disturbance of the sympathetic nervous system may require another type of treatment than inflammation-induced endothelial dysfunction. Diagnostic tools to distinguish these underlying pathophysiological mechanisms of vasomotor disturbances would enable a mechanism-based treatment and improve clinical outcome.

Familial abdominal aortic aneurysm is associated with more complications after endovascular aneurysm repair.

OBJECTIVE: A familial predisposition to abdominal aortic aneurysms (AAAs) is present in approximately one-fifth of patients. Nevertheless, the clinical implications of a positive family history are not known. We investigated the risk of aneurysm-related complications after endovascular aneurysm repair (EVAR) for patients with and without a positive family history of AAA. METHODS: Patients treated with EVAR for intact AAAs in the Erasmus University Medical Center between 2000 and 2012 were included in the study. Family history was obtained by written questionnaire. Familial AAA (fAAA) was defined as patients having at least one first-degree relative affected with aortic aneurysm. The remaining patients were considered sporadic AAA. Cardiovascular risk factors, aneurysm morphology (aneurysm neck, aneurysm sac, and iliac measurements), and follow-up were obtained prospectively. The primary end point was complications after EVAR, a composite of endoleaks, need for secondary interventions, aneurysm sac growth, acute limb ischemia, and postimplantation rupture. Secondary end points were specific components of the primary end point (presence of endoleak, need for secondary intervention, and aneurysm sac growth), aneurysm neck growth, and overall survival. Kaplan-Meier estimates for the primary end point were calculated and compared using log-rank (Mantel-Cox) test of equality. A Cox-regression model was used to calculate the independent risk of complications associated with fAAA. RESULTS: A total of 255 patients were included in the study (88.6% men; age 72 ± 7 years, median follow-up 3.3 years; interquartile range, 2.2-6.1). A total of 51 patients (20.0%) were classified as fAAA. Patients with fAAA were younger (69 vs 72 years; P = .015) and were less likely to have ever smoked (58.8% vs 73.5%; P = .039). Preoperative aneurysm morphology was similar in both groups. Patients with fAAA had significantly more complications after EVAR (35.3% vs 19.1%; P = .013), with a twofold increased risk (adjusted hazard ratio, 2.1; 95% confidence interval, 1.2-3.7). Secondary interventions (39.2% vs 20.1%; P = .004) and aneurysm sac growth (20.8% vs 9.5%; P = .030) were the most important elements accounting for the difference. Furthermore, a trend toward more type I endoleaks during follow-up was observed (15.6% vs 7.4%; P = .063) and no difference in overall survival. CONCLUSIONS: The current study shows that patients with a familial form of AAA develop more aneurysm-related complications after EVAR, despite similar AAA morphology at baseline. These findings suggest that patients with fAAA form a specific subpopulation and create awareness for a possible increase in the risk of complications after EVAR.

Lower atherosclerotic burden in familial abdominal aortic aneurysm.

OBJECTIVE: Despite the apparent familial tendency toward abdominal aortic aneurysm (AAA) formation, the genetic causes and underlying molecular mechanisms are still undefined. In this study, we investigated the association between familial AAA (fAAA) and atherosclerosis. METHODS: Data were collected from a prospective database including AAA patients between 2004 and 2012 in the Erasmus University Medical Center, Rotterdam, The Netherlands. Family history was obtained by written questionnaire (93.1% response rate). Patients were classified as fAAA when at least one affected first-degree relative with an aortic aneurysm was reported. Patients without an affected first-degree relative were classified as sporadic AAA (spAAA). A standardized ultrasound measurement of the common carotid intima-media thickness (CIMT), a marker for generalized atherosclerosis, was routinely performed and patients' clinical characteristics (demographics, aneurysm characteristics, cardiovascular comorbidities and risk factors, and medication use) were recorded. Multivariable linear regression analyses were used to assess the mean adjusted difference in CIMT and multivariable logistic regression analysis was used to calculate associations of increased CIMT and clinical characteristics between fAAA and spAAA. RESULTS: A total of 461 AAA patients (85% men, mean age, 70 years) were included in the study; 103 patients (22.3%) were classified as fAAA and 358 patients (77.7%) as spAAA. The mean (standard deviation) CIMT in patients with fAAA was 0.89 (0.24) mm and 1.00 (0.29) mm in patients with spAAA (P = .001). Adjustment for clinical characteristics showed a mean difference in CIMT of 0.09 mm (95% confidence interval, 0.02-0.15; P = .011) between both groups. Increased CIMT, smoking, hypertension, and diabetes mellitus were all less associated with fAAA compared with spAAA. CONCLUSIONS: The current study shows a lower atherosclerotic burden, as reflected by a lower CIMT, in patients with fAAA compared with patients with spAAA, independent of common atherosclerotic risk factors. These results support the hypothesis that although atherosclerosis is a common underlying feature in patients with aneurysms, atherosclerosis is not the primary driving factor in the development of fAAA.

The tryptophan kynurenine pathway, neopterin and IL-6 during vulvectomy and abdominal hysterectomy.

BACKGROUND: Surgery has wide ranging immunomodulatory properties of which the mechanism is poorly understood. In order to investigate how different types of surgery influence inflammation, we designed a longitudinal observational study investigating two inflammatory profiles of two separate patient groups undergoing gynaecological operations of differing severity. In addition to measuring the well known inflammatory markers neopterin and IL-6, we also determined the kynurenine/tryptophan ratio. This study was a prospective, single center, two-armed observational study involving 28 female patients. Plasma levels of tryptophan, kynurenine, neopterin and IL-6 were determined from samples taken at: 24 hrs pre-operative, prior to induction, ten minutes before the operation was expected to end, and at 24 and 96 hours post operative in patients undergoing abdominal hysterectomy and vulvectomy. RESULTS: There were 15 and 13 patients included in the vulvectomy and abdominal hysterectomy groups, respectively. In this study we show that anesthesia and surgery significantly increases the enzyme activity of indoleamine 2, 3 dioxygenase (IDO) as measured by the kynurenine/tryptophan ratio (P=0.003), while maintaining stable neopterin levels. However, abdominal hysterectomy causes a considerable IL-6 increase (P<0.001). CONCLUSION: Surgery and associated anesthesia cause a significant tryptophan level decrease while significantly increasing IDO activity. Both types of surgery produce nearly identical neopterin time curve relationships, with no significant change occurring in either group. However, even though neopterin is unaffected by the severity of surgery, IL-6 responded to surgical invasiveness by revealing a significant increase during abdominal hysterectomy.

Evaluation of the auditory evoked potentials derived aepEX(™) as a measure of hypnotic depth in pediatric patients receiving sevoflurane-remifentanil anesthesia.

BACKGROUND: The aepEX is a measure of depth of hypnosis (DoH), derived from processed mid-latency auditory evoked potentials. OBJECTIVES: To evaluate the aepEX as a measure of DoH in children receiving sevoflurane-remifentanil anesthesia. METHODS: aepEX and bispectral index (BIS) were recorded simultaneously in 75 children, (1-3, 3-6, and 6-18 years), receiving sevoflurane at endtidal concentrations (ETsevo ) between 1.5 and 0.5 MAC. The ETsevo at which the aepEX and BIS had a value of 50 (EC50aep EX and EC50BIS ) was calculated by nonlinear regression analysis. The accuracy of aepEX and BIS to predict the DoH was assessed by prediction probability (Pk ) and receiver operating characteristics (ROC) analysis. RESULTS: Seventy-four children were included for analysis. The EC50aep EX (2.68%) and EC50BIS (2.10%) were comparable; the same accounts for the EC50aep EX of the different age groups and the EC50aep EX and EC50BIS of corresponding age groups. The EC50BIS in children aged 1-3 years was lower than in the older age groups (P < 0.05). Pk values of the aepEX (0.32, CI 95% 0.08-0.56) and BIS (0.47, CI 95% 0.19-0.75) were comparable. The area under the ROC curve was 0.72 (CI 95%: 0.62-0.82) and 0.67 (CI95%: 0.56-0.77) for the aepEX and BIS, respectively (P = 0.54). Optimal cutoff values were >60 (aepEX) and >68 (BIS), with corresponding specificities 91%, CI 95%: 80-97% (aepEX) and 66%, CI 95%: 52-77% (BIS). CONCLUSIONS: In this study with children receiving sevoflurane anesthesia, the aepEX outperformed the BIS in distinguishing unconsciousness from consciousness. Both indices performed equally bad in differentiating different levels of DoH.

Opportunities and barriers for prehospital emergency medical services research in the Netherlands; results of a mixed-methods consensus study.

INTRODUCTION: Quality improvement in prehospital emergency medical services (EMS) can only be achieved by high-quality research and critical appraisal of current practices. This study examines current opportunities and barriers in EMS research in the Netherlands. METHODS: This mixed-methods consensus study consisted of three phases. The first phase consisted of semi-structured interviews with relevant stakeholders. Thematic analysis of qualitative data derived from these interviews was used to identify main themes, which were subsequently discussed in several online focus groups in the second phase. Output from these discussions was used to shape statements for an online Delphi consensus study among relevant stakeholders in EMS research. Consensus was met if 80% of respondents agreed or disagreed on a particular statement. RESULTS: Forty-nine stakeholders participated in the study; qualitative thematic analysis of the interviews and focus group discussions identified four main themes: (1) data registration and data sharing, (2) laws and regulations, (3) financial aspects and funding, and (4) organization and culture. Qualitative data from the first two phases of the study were used to construct 33 statements for an online Delphi study. Consensus was reached on 21 (64%) statements. Eleven (52%) of these statements pertained to the storage and use of EMS patient data. CONCLUSION: Barriers for prehospital EMS research in the Netherlands include issues regarding the use of patient data, privacy and legislation, funding and research culture in EMS organizations. Opportunities to increase scientific productivity in EMS research include the development of a national strategy for EMS data and the incorporation of EMS topics in research agendas of national medical professional associations.

Effect of major and minor surgery on plasma levels of arginine, citrulline, nitric oxide metabolites, and ornithine in humans.

OBJECTIVE: To determine the effect of surgical invasiveness on plasma levels of arginine, citrulline, ornithine, and nitric oxide (NO) in humans. BACKGROUND: Surgical trauma may have a profound effect on the metabolism of NO. However, human studies reported both increased and decreased NO levels after hemorrhagic shock. Arginine, citrulline, and ornithine are key amino acids involved in NO metabolism, but studies evaluating these amino acids together with NO and during 2 types of surgery are lacking. This study tests the hypothesis that major surgery has a more profound effect on plasma levels of arginine, citrulline, NO, and ornithine than minor surgery. METHODS: Fifteen patients undergoing minor surgery (vulvectomy) and 13 patients undergoing major surgery (laparotomy) were prospectively followed up for 4 days. Plasma was collected for evaluation of levels of arginine, citrulline, NO, and ornithine. RESULTS: Throughout the experiment, arginine levels did not significantly differ between experimental groups. Perioperative plasma citrulline levels were significantly lower in the laparotomy group than in the vulvectomy group, whereas both groups showed a decrease in citrulline levels at the end of the operation and 24 hours postoperatively. Roughly the same pattern was seen for plasma NO and ornithine levels. However, ornithine levels in the laparotomy group showed a more drastic decrease at the end of the operation and 24 hours postoperatively than citrulline and NO levels. CONCLUSIONS: The level of surgical invasiveness has the most profound effect on plasma levels of ornithine. In addition, heavier surgical trauma is paired with lower postoperative levels of citrulline and NO metabolites than lighter surgery. It is suggested that surgical trauma stimulates the laparotomy group to consume significantly more ornithine, possibly for use in wound healing.

Adequate seal and no endoleak on the first postoperative computed tomography angiography as criteria for no additional imaging up to 5 years after endovascular aneurysm repair.

OBJECTIVE: Intensive image surveillance after endovascular aneurysm repair is generally recommended due to continued risk of complications. However, patients at lower risk may not benefit from this strategy. We evaluated the predictive value of the first postoperative computed tomography angiography (CTA) characteristics for aneurysm-related adverse events as a means of patient selection for risk-adapted surveillance. METHODS: All patients treated with the Low-Permeability Excluder Endoprosthesis (W. L. Gore & Assoc, Flagstaff, Ariz) at a tertiary institution from 2004 to 2011 were included. First postoperative CTAs were analyzed for the presence of endoleaks, endograft kinking, distance from the lowermost renal artery to the start of the endograft, and for proximal and distal sealing length using center lumen line reconstructions. The primary end point was freedom from aneurysm-related adverse events. Multivariable Cox regression was used to test postoperative CTA characteristics as independent risk factors, which were subsequently used as selection criteria for low-risk and high-risk groups. Estimates for freedom from adverse events were obtained using Kaplan-Meier survival curves. RESULTS: Included were 131 patients. The median follow-up was 4.1 years (interquartile range, 2.1-6.1). During this period, 30 patients (23%) sustained aneurysm-related adverse events. Seal length <10 mm and presence of endoleak were significant risk factors for this end point. Patients were subsequently categorized as low-risk (proximal and distal seal length ≥10 mm and no endoleak, n = 62) or high-risk (seal length <10 mm or presence of endoleak, or both; n = 69). During follow-up, four low-risk patients (3%) and 26 high-risk patients (19%) sustained events (P < .001). Four secondary interventions were required in three low-risk patients, and 31 secondary interventions in 23 high-risk patients. Sac growth was observed in two low-risk patients and in 15 high-risk patients. The 5-year estimates for freedom from aneurysm-related adverse events were 98% for the low-risk group and 52% for the high-risk group. For each diagnosis, 81.7 image examinations were necessary in the low-risk group and 8.2 in the high-risk group. CONCLUSIONS: Our results suggest that the first postoperative CTA provides important information for risk stratification after endovascular aneurysm repair when the Excluder endoprosthesis is used. In patients with adequate seal and no endoleaks, the risk of aneurysm-related adverse events was significantly reduced, resulting in a large number of unnecessary image examinations. Adjusting the imaging protocol beyond 30 days and up to 5 years, based on individual patients' risk, may result in a more efficient and rational postoperative surveillance.

Aneurysmal disease is associated with lower carotid intima-media thickness than occlusive arterial disease.

OBJECTIVE: Patients with aneurysmal and occlusive arterial disease have overlapping cardiovascular risk profiles. The question remains how atherosclerosis is related to the formation of aortic aneurysms. Common carotid artery intima-media thickness (CIMT) is an easily accessible and objective marker of early atherosclerosis. The aim of the current study was to investigate whether there is a difference in atherosclerotic burden as measured by CIMT between patients with aneurysmal and those with occlusive arterial disease. METHODS: From 2004 to 2011, the CIMT was measured using B-mode ultrasound scanning in patients undergoing vascular surgery for aortic aneurysmal or occlusive arterial disease at the Erasmus University Medical Center. Cardiovascular risk factors, comorbidities, and medication were recorded. Patients treated for combined aneurysmal and occlusive arterial disease and patients diagnosed with a genetic aneurysm syndrome were excluded. Univariable and multivariable analyses were used to calculate differences in CIMT between aneurysmal and occlusive arterial disease. RESULTS: In total, 904 patients were included in the study: 502 patients with aneurysmal disease (85% male; mean age, 72 years) and 402 patients with occlusive arterial disease (65% male; mean age, 64 years). The mean (standard deviation) CIMT in patients with aneurysmal disease was 0.97 (0.29) mm and was 1.07 (0.38) mm in patients with occlusive arterial disease (P < .001). Adjustment for cardiovascular risk factors, comorbidities, and medication showed a mean difference in CIMT of 0.15 mm (95% confidence interval, 0.10-0.20; P < .001). CONCLUSIONS: The current study shows a lower CIMT in patients with aneurysmal disease than in those with occlusive arterial disease, indicating a lower atherosclerotic burden in patients with aneurysmal disease. These findings endorse the idea that additional pathogenic mechanisms are involved in aortic aneurysm formation. Further studies are needed to clarify the role of atherosclerosis in aortic aneurysm formation.