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1.  Variation in postoperative non-steroidal anti-inflammatory analgesic use after colorectal surgery: a database analysis 
BMC Anesthesiology  2014;14:18.
Non-steroid anti-inflammatory drugs (NSAIDs) have been proposed as part of a multimodal postoperative analgesia in patients operated for colorectal cancer. However, whether these drugs are prescribed and taken by the patients have not been evaluated. The aim of this study was to quantify the postoperative use of NSAIDs in these patients.
Data from patients operated for colorectal cancer between January 1, 2006 and December 31, 2009 were collected from the Danish Colorectal Cancer Group’s (DCCG) prospective database. From the electronically registered medical records, data for the use of the two NSAIDs diclofenac and ibuprofen were recorded. The data from six colorectal departments in eastern Denmark were compared.
Of the 2,754 patients analyzed overall, 40.6% received NSAIDs as part of their analgesic treatment. The percentage of the patients receiving NSAIDs, receiving a pre-defined dosage as a minimum and receiving NSAIDs as p.r.n. medication, and the type of NSAID were significantly different both between department and within departments. The median dose of ibuprofen and diclofenac were 1200 mg (400–2,400 mg) and 100 mg (50–200 mg), respectively.
The large variation between and within the departments points to an inconsistency in the use of multimodal post-operative pain treatments. This may be a result of insufficient evidence on procedure specific pain treatments and possibly a lack of compliance to existing guidelines. High-quality large-scale studies are warranted to form the basis for guidelines for postoperative analgesic treatment.
PMCID: PMC3976552  PMID: 24649938
Postoperative analgesia; Non-steroid anti-inflammatory drugs; NSAIDs; Multimodal analgesia; Pain treatment
2.  Usefulness of N-terminal pro-B-type natriuretic peptide in patients admitted to the intensive care unit: a multicenter prospective observational study 
BMC Anesthesiology  2014;14:16.
The role of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) as a prognostic factor in patients admitted to the intensive care unit (ICU) is not yet fully established. We aimed to determine whether NT-pro-BNP is predictive of ICU mortality in a multicenter cohort of critically ill patients.
A total of 1440 patients admitted to 22 ICUs (medical, 14; surgical, six; multidisciplinary, two) in 15 tertiary or university-affiliated hospitals between July 2010 and January 2011 were assessed. Patient data, including NT-pro-BNP levels and Simplified Acute Physiology Score (SAPS) 3 scores, were recorded prospectively in a web-based database.
The median age was 64 years (range, 53–73 years), and 906 (62.9%) patients were male. The median NT-pro-BNP level was 341 pg/mL (104–1,637 pg/mL), and the median SAPS 3 score was 57 (range, 47–69). The ICU mortality rate was 18.9%, and hospital mortality was 24.5%. Hospital survivors showed significantly lower NT-pro-BNP values than nonsurvivors (245 pg/mL [range, 82–1,053 pg/mL] vs. 875 pg/mL [241–5,000 pg/mL], respectively; p < 0.001). In prediction of hospital mortality, the area under the curve (AUC) for NT-pro-BNP was 0.67 (95% confidence interval [CI], 0.64–0.70) and SAPS 3 score was 0.83 (95% CI, 0.81–0.85). AUC increment by adding NT-pro-BNP is minimal and likely no different to SAPS 3 alone.
The NT-pro-BNP level was more elevated in nonsurvivors in a multicenter cohort of critically ill patients. However, there was little additional prognostic power when adding NT-pro-BNP to SAPS 3 score.
PMCID: PMC3975327  PMID: 24612820
N-terminal pro-B-type natriuretic peptide; Intensive care unit; Critical care; Prognosis
3.  Isoflurane reduces hypoxia/reoxygenation-induced apoptosis and mitochondrial permeability transition in rat primary cultured cardiocytes 
BMC Anesthesiology  2014;14:17.
The volatile anesthetic isoflurane protects the heart from hypoxia/reperfusion (H/R) injury. However, it is still incompletely understood whether isoflurane exerts its protective role through preventing mitochondrial permeability transition pore (MPTP) opening.
Primary cultured cardiocytes were exposed to H/R in the absence or presence of isoflurane. Cell cytotoxicity and apoptosis were detected by MTT assay and TUNEL staining, respectively. MPTP function was monitored by confocal imaging after reoxygenation. ROS production and activation of caspase-3 were determined by fluorescent reader and western blot, respectively.
As compared to the control group, H/R led to significant cell cytotoxicity and apoptosis, while application of isoflurane markedly reversed the effects. Furthermore, isoflurane significantly inhibits the formation of H/R-induced excess ROS production. Finally, isoflurane attenuated the onset of mitochondrial permeability transition pore (MPTP) occurred during hypoxia/reoxygenation, and in turn inhibited activation of caspase-3.
These data indicate that isoflurane has a protective effect on cardiocytes exposed to H/R by reducing excess ROS production, blocking open of MPTP and further reducing apoptosis.
PMCID: PMC3975578  PMID: 24612850
Isoflurane; Hypoxia/reoxygenation; Cardiocyte; Apoptosis; Mitochondrial permeability transition; ROS
4.  Development, validation, and results of a survey to measure understanding of cardiopulmonary resuscitation choices among ICU patients and their surrogate decision makers 
BMC Anesthesiology  2014;14:15.
Shared-decision-making about resuscitation goals of care for intensive care unit (ICU) patients depends on a basic understanding of cardiopulmonary resuscitation (CPR). Our objective was to develop and validate a survey to assess comprehension of CPR among ICU patients and surrogate decision-makers.
We developed a 12-item verbally-administered survey incorporating input from patients, clinicians, and expert focus groups.
We administered the survey to 32 ICU patients and 37 surrogates, as well as to 20 resident physicians to test discriminative validity. Median (interquartile range) total knowledge scores were 7 (5-10) for patients, 9 (7-12) for surrogates, and 14.5 (14-15) for physicians (p <.001). Forty-four percent of patients and 24% of surrogates could not explain the purpose of CPR. Eighty-eight percent of patients and 73% of surrogates could not name chest compressions and breathing assistance as two components of CPR in the hospital. Forty-one percent of patients and 24% of surrogates could not name a single possible complication of CPR. Forty-three percent of participants could not specify that CPR would be performed with a full code order and 25% of participants could not specify that CPR would not be performed with a do-not-resuscitate order. Internal consistency (Cronbach’s alpha = 0.97) and test-retest reliability (Pearson correlation = 0.96, p < .001) were high.
This easily administered survey, developed to measure knowledge of CPR and resuscitation preference options among ICU patients and surrogates, showed strong face validity, content validity, internal consistency, test-retest reliability, and discriminative validity. A substantial proportion of ICU patients and surrogates decision-makers have poor knowledge of CPR and basic resuscitation options.
PMCID: PMC3975319  PMID: 24606839
Cardiopulmonary resuscitation; Questionnaires; Health knowledge; Intensive care unit
5.  The effect of succinylcholine on malignant hyperthermia events in susceptible swine 
BMC Anesthesiology  2014;14:14.
While the impact of volatile anaesthetics to induce malignant hyperthermia (MH) is abundantly clear, the role of succinylcholine still remains controversial. To evaluate the influence of succinylcholine on porcine MH events, the authors investigated the hemodynamic and metabolic responses in MH susceptible (MHS) and non-susceptible (MHN) swine following either succinylcholine or halothane application alone or a combination of both substances.
With approval of the local animal care committee 27 MHS and 30 MHN pigs were anaesthetized and mechanically ventilated. Fiberoptic probes for continuous PCO2 measurement were inserted into the femoral vein and the triceps muscle. Group A received succinylcholine 4 mg/kg, group B incremental doses of halothane (0.5, 1.0 vol%) and group C succinylcholine and halothane simultaneously. Vital signs were recorded continuously.
Prior to drug application measured values did not differ between MHS and MHN. While MHN pigs did not show relevant alterations, succinylcholine, halothane and the combination of both lead to significant hemodynamic and metabolic changes in MHS swine.
Hemodynamic and metabolic alterations following succinylcholine were similar to halothane in MHS pigs. The combination of both pharmacological agents potentiated the observed effects. According to these results succinylcholine acted as an independent and supportive factor during onset of an MH episode.
PMCID: PMC3973851  PMID: 24606822
Malignant hyperthermia; Succinylcholine; Halothane; Swine
6.  Efficacy and safety of ondansetron in preventing postanesthesia shivering: a meta-analysis of randomized controlled trials 
BMC Anesthesiology  2014;14:12.
Shivering is a very common complication in the postanesthesia period. Increasing studies have reported ondansetron may be effective in prevention of postanesthesia shivering (PAS). However, the results remained controversial; hence we conducted a meta-analysis of randomized controlled trials to evaluate the efficacy and safety of ondansetron on the prevention of postanesthesia shivering.
PubMed and Embase databases were searched to identify the eligible randomized controlled trials assessing the effect of ondansetron on the prevention of PAS. Results were expressed as risk ratios (RRs) with accompanying 95% confidence intervals (CIs). The meta-analysis was performed with fixed-effect model or random-effect model according to the heterogeneity.
Six trials including 533 subjects were included. Compared with placebo, ondansetron was associated with a significant reduction of PAS (RR 0.43, 95% CI, 0.27-0.70), without an increased risk of bradycardia (RR 0.37, 95% CI, 0.12-1.15). Compared with meperidine, no difference was observed in the incidence of PAS (RR 0.68, 95% CI, 0.39-1.19) and bradycardia (RR 2.0, 95% CI, 0.38-10.64).
Ondansetron has a preventive effect on PAS without a paralleled side effect of bradycardia.
PMCID: PMC3945808  PMID: 24588846
Qndansetron; Postanesthesia shivering; Meta-analysis
7.  Comparison of the glidescope®, flexible fibreoptic intubating bronchoscope, iPhone modified bronchoscope, and the Macintosh laryngoscope in normal and difficult airways: a manikin study 
BMC Anesthesiology  2014;14:10.
Smart phone technology is becoming increasingly integrated into medical care.
Our study compared an iPhone modified flexible fibreoptic bronchoscope as an intubation aid and clinical teaching tool with an unmodified bronchoscope, Glidescope® and Macintosh laryngoscope in a simulated normal and difficult airway scenario.
Sixty three anaesthesia providers, 21 consultant anaesthetists, 21 registrars and 21 anaesthetic nurses attempted to intubate a MegaCode Kelly™ manikin, comparing a normal and difficult airway scenario for each device. Primary endpoints were time to view the vocal cords (TVC), time to successful intubation (TSI) and number of failed intubations with each device. Secondary outcomes included participant rated device usability and preference for each scenario. Advantages and disadvantages of the iPhone modified bronchoscope were also discussed.
There was no significant difference in TVC with the iPhone modified bronchoscope compared with the Macintosh blade (P = 1.0) or unmodified bronchoscope (P = 0.155). TVC was significantly shorter with the Glidescope compared with the Macintosh blade (P < 0.001), iPhone (P < 0.001) and unmodified bronchoscope (P = 0.011). The iPhone bronchoscope TSI was significantly longer than all other devices (P < 0.001). There was no difference between anaesthetic consultant or registrar TVC (P = 1.0) or TSI (P = 0.252), with both being less than the nurses (P < 0.001). Consultant anaesthetists and nurses had a higher intubation failure rate with the iPhone modified bronchoscope compared with the registrars. Although more difficult to use, similar proportions of consultants (14/21), registrars (15/21) and nurses (15/21) indicated that they would be prepared to use the iPhone modified bronchoscope in their clinical practice. The Glidescope was rated easiest to use (P < 0.001) and was the preferred device by all participants for the difficult airway scenario.
The iPhone modified bronchoscope, in its current configuration, was found to be more difficult to use compared with the Glidescope® and unmodified bronchoscope; however it offered several advantages for teaching fibreoptic intubation technique when video-assisted bronchoscopy was unavailable.
PMCID: PMC3945614  PMID: 24575885
8.  The influence of the direction of J-tip on the placement of a subclavian catheter: real time ultrasound-guided cannulation versus landmark method, a randomized controlled trial 
BMC Anesthesiology  2014;14:11.
It has been reported that the direction of the guidewire J-tip is associated with misplacement of a central venous catheter. We hypothesized that real-time ultrasound-guided infraclavicular subclavian venous cannulation would be less influenced by the direction of guidewire J-tip compared to landmark method.
Sixty adult patients who required subclavian venous catheterization for neurosurgery were enrolled in this prospective randomized controlled study. Patients were randomly divided into a landmark group (n = 30) or an ultrasound group (n = 30). After the subclavian vein was punctured, the guidewire was advanced with the guidewire J-tip directed cephalad. Misplacement or advancement failure of the guidewire was regarded as an unsuccessful placement. Postoperative chest radiography was performed to confirm pneumothorax and the location of the catheter tip.
The two groups were comparable with respect to age, gender, height, and weight distribution. The incidence of unsuccessful guidewire placement was lower in the ultrasound group than in the landmark group (13% vs. 47%, P = 0.01). Among the unsuccessful guidewire placements, the incidence of misplacement were comparable between the groups and were all located in the ipsilateral internal jugular vein (7% vs. 7%). However, the incidence of advancement failure was significantly higher in landmark group (40% vs. 7%, P = 0.005). There were no complications such as pneumothorax or hemothorax.
The proper placement of guidewire was less influenced by the direction of the guidewire J-tip with ultrasound-guided subclavian venous cannulation than with the landmark approach.
PMCID: PMC3975933  PMID: 24581318
Central venous catheterization; Subclavian vein; Ultrasound
9.  Procalcitonin as a marker of Candida species detection by blood culture and polymerase chain reaction in septic patients 
BMC Anesthesiology  2014;14:9.
The aim of our study is to test procalcitonin (PCT) as surrogate marker of identification of Candida spp. by blood culture (BC) and real-time-polymerase chain reaction (PCR), whether alone or in association with bacteria, in septic patients.
We performed a single-centre retrospective study. We reviewed the clinical charts of patients with a diagnosis of severe sepsis or septic shock treated at our general intensive care unit from March 2009 to March 2013. We analysed all diagnostic episodes consisting of BC, real-time PCR assay and dosage of PCT. We registered age, sex, white blood count, sequential organ failure assessment score and type of admission between medical or surgical. When inclusion criteria were met more than once, we registered the new diagnostic episode as subsequent diagnostic episode. The diagnostic performance of PCT to predict Candida spp. identification alone or in mixed infections by either BC or PCR was tested using the receiver-operative characteristic curve. Logistic regression was constructed using presence of Candida spp. as the dependent variable.
A total of 260 diagnostic episodes met the inclusion criteria. According to BC results classification, a significantly lower value of PCT was observed in Candida spp. BSI (0.99 ng/ml, 0.86 - 1.34) than in BSI caused by bacteria (16.7 ng/ml, 7.65 - 50.2) or in mixed infections (4.76 ng/ml, 2.98 - 6.08). Similar findings were observed considering PCR results. A cut-off of ≤ 6.08 ng/ml for PCT yielded a sensitivity of 86.8%, a specificity of 87.4%, a positive predictive value of 63.9%, a negative predictive value (NPV) of 96.3% and an area under the curve of 0.93 for Candida spp. identification by BC. A similar high NPV for a cut-off ≤ 6.78 ng/ml was observed considering the classification of diagnostic episodes according to PCR results, with an AUC of 0.85. A subsequent diagnostic episode was independently associated with Candida spp. detection either by BC or PCR.
PCT could represent a useful diagnostic tool to exclude the detection of Candida spp. by BC and PCR in septic patients.
PMCID: PMC3936855  PMID: 24559080
Procalcitonin; Sepsis; Candida species; Blood stream infection; Fungal infection; Polymerase chain reaction; Antifungal therapy
10.  Catheter-based distal sciatic nerve block in patients with Charcot-Marie-Tooth disease 
BMC Anesthesiology  2014;14:8.
The use of peripheral nerve blocks in patients with Charcot-Marie-Tooth (CMT) disease is scarcely reported; however, when performed it has proven to be effective for postoperative pain control.
A distal catheter-based sciatic nerve block for postoperative pain control was offered to 27 consecutive CMT patients scheduled for elective foot surgery. 18 of the 27 CMT patients consented to the offered sciatic nerve block. Localization of the sciatic nerve was guided by a nerve stimulator. The threshold current required to generate a motor response was assessed and a catheter inserted. Postoperative pain was assessed by recording the dose of analgesics to maintain visual analog score < 3 the next 48 hours. On demand patients received boluses of ropivacaine (2 mg/mL) via the catheter and/or analgesics in case of insufficient pain relief. Total postoperative ropivacaine dosage and analgesic consumption were recorded. About one year after the block patients were contacted to report their actual status by self-assessment.
In 17 patients a catheter could be placed. In 7 patients placement of the catheter was difficult (several attempts, high electrical impedance). Patients with nerve block had lower analgesics consumption compared to patients without a block. Surprisingly, the 7 patients with “difficult” catheter-placement had the overall lowest ropivacaine and analgesics consumption compared to all other patients with or without peripheral block. No anesthesia related complications were reported by the questionnaire.
In our small series catheter-based distal sciatic block within CMT patients had safely been used for pain relief up to three days. The infusion of local anesthetics via a catheter was not associated with any complication.
PMCID: PMC3928914  PMID: 24524338
Charcot-Marie-Tooth disease; Peripheral neuropathies; Peripheral nerve block
11.  BMC Anesthesiology reviewer acknowledgement, 2013 
BMC Anesthesiology  2014;14:7.
Contributing reviewers
The editors of BMC Anesthesiology would like to thank all our reviewers who have contributed their time to the journal in Volume 13 (2013).
PMCID: PMC3923558  PMID: 24524310
12.  A comparison of three techniques (local anesthetic deposited circumferential to vs. above vs. below the nerve) for ultrasound guided femoral nerve block 
BMC Anesthesiology  2014;14:6.
Fractured neck of femur generally requires operative fixation and is a common cause of admission to hospital. The combination of femoral nerve block and spinal anesthesia is a common anesthetic technique used to facilitate the surgical procedure. The optimal disposition of local anesthetic (LA) relative the femoral nerve (FN) has not been defined. Our hypothesis was: that the deposition of LA relative to the FN influences the quality of analgesia for positioning of the patient for performance of spinal anesthesia. The primary outcome was verbal rating (VRS) pain scores 0–10 assessed immediately after positioning the patient to perform spinal anesthesia.
With Institutional ethical approval and having obtained written informed consent from each, 52 patients were studied. The study was registered with (NCT01527812). Patients were randomly allocated to undergo to one of three groups namely: intention to deposit lidocaine 2% (15 ml) i. above (Group A), ii. below (Group B), iii. circumferential (Group C) to the FN. A blinded observer assessed i. the sensory nerve block (cold) in the areas of the terminal branches of the FN and ii. VRS pain scores on passive movement from block completion at 5 minutes intervals for 30 minutes. Immediately after positioning the patient for spinal anesthesia, VRS pain scores were recorded.
Pain VRS scores during positioning were similar in the three groups [Above group/Below group/Circumferential group: 2(0–9)/0(0–10)/3(0–10), median(range), p:0.32]. The block was deemed to have failed in 20%, 47% and 12% in the Above group, Below group and Circumferential group respectively. The median number of needle passes was greater in the Circumferential group compared with the Above group (p:0.009). Patient satisfaction was greatest in the Circumferential group [mean satisfaction scores were 83.5(19.8)/88.1(20.5)/93.8(12.3), [mean(SD), p=0.04] in the Above, Below and Circumferential groups respectively.
We conclude that there is no clinical advantage to attempting to deposit LA circumferential to the femoral nerve (relative to depositing LA either above or below the nerve), during femoral nerve block in this setting.
PMCID: PMC3933203  PMID: 24460975
Optimal positioning of the local anesthetic; Femoral nerve block
13.  Potential side effect of propofol and sevoflurane for anesthesia of anti-NMDA-R encephalitis 
BMC Anesthesiology  2014;14:5.
Many anesthetic drugs interact with the NMDA receptor and may therefore alter the clinical presentation of anti-NMDA-R encephalitis.
Case presentation
A 24-year-old woman was admitted to hospital for decreased consciousness and hyperthermia. Cerebrospinal fluid analysis revealed lymphocytic pleocytosis, and elevated protein. Cultures were negative. Patient state worsened with agitation, facial dyskinesia, ocular deviation, and limb dystonia. Diagnosis of anti-NMDA-R encephalitis was evidenced by specific antibodies. High doses of methylprednisolone were administered. CT scan disclosed an ovarian teratoma and tumor resection was scheduled under anesthesia with propofol, sufentanil, atracurium and sevoflurane. Sedation after surgery was maintained with propofol. Rapidly after surgery, patient’s condition deteriorated with increase of dyskinesias, and two tonic-clonic generalized seizure events.
In patients with anti-NMDA-R encephalitis, anesthesia using benzodiazepines, opiates and curares, which fail to interfere with the NMDA pathway, should be preferred.
PMCID: PMC3899925  PMID: 24433363
Encephalitis; General anesthesia; NMDA; Propofol; Sevoflurane
14.  Proteomic profiling of the phosphoproteins in the rat thalamus, hippocampus and frontal lobe after propofol anesthesia 
BMC Anesthesiology  2014;14:3.
Propofol is a safe and effective intravenous anesthetic that is widely used for the induction and maintenance of anesthesia during surgery. However, the mechanism by which propofol exerts its anesthetic effect remains unknown. The rapid onset of phosphorylation modifications coincides with that of propofol anesthesia.
Propofol-anesthetized rat models were built and phosphorylated proteins in the thalamus, hippocampus and frontal lobe were enriched the to analyze the changes in these phosphoproteins after propofol anesthesia.
Sixteen of these phosphoprotein spots were successfully identified using MALDI-TOF MS and a subsequent comparative sequence search in the Mascot database. Of these proteins, keratin 18 and the tubulin 2c chain are cytoskeletal proteins; keratin 18 and gelsolin are relevant to alcohol drowsiness. Based on Western blot analysis, we also confirmed that the phosphorylation of these proteins is directly induced by propofol, indicating that propofol anesthesia may be relevant to cytoskeletal proteins and alcohol drowsiness.
These identified propofol-induced phosphorylations of proteins provide meaningful contributions for further studying the anesthetic mechanism of propofol.
PMCID: PMC3922749  PMID: 24410762
2D-gel electrophoresis; Anesthesia; Phosphorylation; Propofol; Rats
15.  The effect of changing the sequence of cuff inflation and device fixation with the LMA-Supreme® on device position, ventilatory complications, and airway morbidity: a clinical and fiberscopic study 
BMC Anesthesiology  2014;14:2.
The conventional sequence when using supraglottic airway devices is insertion, cuff inflation and fixation. Our hypothesis was that a tighter fit of the cuff and tip could be achieved with a consequently lower incidence of air leak, better separation of gastrointestinal and respiratory tracts and less airway morbidity if the device were first affixed and the cuff then inflated.
Our clinical review board approved the study (public registry number DRKS00003174). An LMA Supreme® was inserted into 184 patients undergoing lower limb arthroscopy in propofol-remifentanil anaesthesia who were randomly assigned to either the control (inflation then fixation; n = 92) or study group (fixation then inflation; n = 92). The cuff was inflated to 60 cmH2O. The patients’ lungs were ventilated in pressure-controlled mode with 5 cmH2O PEEP, Pmax to give 6 ml kg-1 tidal volume, and respiratory rate adjusted to end-tidal CO2 of 4.8 and 5.6 kPa. Correct cuff and tip position were determined by leak detection, capnometry trace, oropharyngeal leak pressure, suprasternal notch test, and lube-tube test. Bowl and cuff position and the presence of glottic narrowing were assessed by fiberscopic examination. Postoperative dysphagia, hoarseness and sore throat were assessed with a questionnaire. Ventilatory impairment was defined as a tidal volume < 6 ml kg-1 with Pmax at oropharyngeal leak pressure, glottic narrowing was defined as an angle between the vocal cords under 16 degrees.
The incidence of incorrect device position (18% vs. 21%), failed ventilation (10% vs. 9%), leak pressure (24.8 vs. 25.2 cmH2O, p = 0.63), failed lube-tube test (16.3% vs. 17.6%) and glottic narrowing (19.3% vs. 14.1%, p = 0.35) was similar in both groups (control vs. study, resp.). When glottic narrowing occurred, it was more frequently associated with ventilatory impairment in the control group (77% vs. 39%; p = 0.04). Airway morbidity was more common in the control group (33% vs. 19%; p < 0.05).
Altering the sequence of cuff inflation and device fixation does not affect device position, oropharyngeal leak pressures or separation of gastrointestinal and respiratory tracts. It reduces the incidence of glottic narrowing with impaired ventilation and also perioperative airway morbidity.
PMCID: PMC3890616  PMID: 24387685
Supraglottic airway; Insertion sequence; Malposition; Endoscopic evaluation; Glottic narrowing; Ventilatory impairment; Airway morbidity
16.  Identifying which septic patients have increased mortality risk using severity scores: a cohort study 
BMC Anesthesiology  2014;14:1.
Early aggressive therapy can reduce the mortality associated with severe sepsis but this relies on prompt recognition, which is hindered by variation among published severity criteria. Our aim was to test the performance of different severity scores in predicting mortality among a cohort of hospital inpatients with sepsis.
We anonymously linked routine outcome data to a cohort of prospectively identified adult hospital inpatients with sepsis, and used logistic regression to identify associations between mortality and demographic variables, clinical factors including blood culture results, and six sets of severity criteria. We calculated performance characteristics, including area under receiver operating characteristic curves (AUROC), of each set of severity criteria in predicting mortality.
Overall mortality was 19.4% (124/640) at 30 days after sepsis onset. In adjusted analysis, older age (odds ratio 5.79 (95% CI 2.87-11.70) for ≥80y versus <60y), having been admitted as an emergency (OR 3.91 (1.31-11.70) versus electively), and longer inpatient stay prior to sepsis onset (OR 2.90 (1.41-5.94) for >21d versus <4d), were associated with increased 30 day mortality. Being in a surgical or orthopaedic, versus medical, ward was associated with lower mortality (OR 0.47 (0.27-0.81) and 0.26 (0.11-0.63), respectively). Blood culture results (positive vs. negative) were not significantly association with mortality. All severity scores predicted mortality but performance varied. The CURB65 community-acquired pneumonia severity score had the best performance characteristics (sensitivity 81%, specificity 52%, positive predictive value 29%, negative predictive value 92%, for 30 day mortality), including having the largest AUROC curve (0.72, 95% CI 0.67-0.77).
The CURB65 pneumonia severity score outperformed five other severity scores in predicting risk of death among a cohort of hospital inpatients with sepsis. The utility of the CURB65 score for risk-stratifying patients with sepsis in clinical practice will depend on replicating these findings in a validation cohort including patients with sepsis on admission to hospital.
PMCID: PMC3918178  PMID: 24383430
Sepsis; Severity; Risk scores; Outcomes; Mortality; CURB; CURB65; Systemic inflammatory response syndrome; SIRS
17.  Efficiency of a pneumatic device in controlling cuff pressure of polyurethane-cuffed tracheal tubes: a randomized controlled study 
BMC Anesthesiology  2013;13:50.
The primary objective of this study was to determine the efficiency of a pneumatic device in controlling cuff pressure (Pcuff) in patients intubated with polyurethane-cuffed tracheal tubes. Secondary objectives were to determine the impact of continuous control of Pcuff, and cuff shape on microaspiration of gastric contents.
Prospective randomized controlled study. All patients requiring intubation and mechanical ventilation ≥48 h were eligible. The first 32 patients were intubated with tapered polyurethane-cuffed, and the 32 following patients were intubated with cylindrical polyurethane-cuffed tracheal tubes. Patients randomly received 24 h of continuous control of Pcuff using a pneumatic device (Nosten®), and 24 h of routine care of Pcuff using a manometer. Target Pcuff was 25 cmH2O. Pcuff was continuously recorded, and pepsin was quantitatively measured in all tracheal aspirates during these periods.
The pneumatic device was efficient in controlling Pcuff (med [IQ] 26 [24, 28] vs 22 [20, 28] cmH2O, during continuous control of Pcuff and routine care, respectively; p = 0.017). In addition, percentage of patients with underinflation (31% vs 68%) or overinflation (53% vs 100%) of tracheal cuff, and percentage of time spent with underinflation (0.9 [0, 17] vs 14% [4, 30]) or overinflation (0 [0, 2] vs 32% [9, 54]) were significantly (p < 0.001) reduced during continuous control of Pcuff compared with routine care.
No significant difference was found in microaspiration of gastric content between continuous control of Pcuff compared with routine care, or between patients intubated with tapered compared with cylindrical polyurethane-cuffed tracheal tubes.
The pneumatic device was efficient in controlling Pcuff in critically ill patients intubated with polyurethane-cuffed tracheal tubes.
Trial registration
The Australian New Zealand Clinical Trials Registry (NCT01351259)
PMCID: PMC3877974  PMID: 24369057
Intubation; Polyurethane; Tracheal cuff; Microaspiration; Tracheal injury; Pneumonia
18.  Functional evaluation and practice survey to guide purchasing of intravenous cannulae 
BMC Anesthesiology  2013;13:49.
There are wide variations in the physical designs and attributes between different brands of intravenous cannulae that makes product selection and purchasing difficult. In a systematic assessment to guide purchasing, we assessed two cannulae – Cannula P and I. We proposed that the results of in-vitro performance testing of the cannulae would be associated with preference after clinical comparison.
We designed an observer-blinded randomised head-to-head trial between the 18, 20 and 22 gauge versions of Cannula P and I. Our primary end-point was pressure (mmHg) generated during various flow rates and our secondary end-point was the force (Newton) required to slide the catheter away from the needle. This was followed by a prospective electronic survey following a two-week clinical trial period.
The mean difference in resistance between Cannula P and I was: 307 (95% CI: 289–325, p < 0.001) for 22G; 135 (95% CI: 125–144, p < 0.001) for 20G; and 27 (95% CI: 26–28, p < 0.001) for 18G. The mean difference in the force needed to displace the catheter away from its needle was: 1.41 N (95% CI: 1.09-1.73, p < 0.001) for 22G; 0.19 N (95% CI: -0.04-0.41, p = 0.12) for 20G; and 1.96 N (95% CI: 1.40-2.52, p < 0.001) for 18G. After a trial period, all 16 anaesthetist who had used both cannulae preferred Cannula I to P.
The evaluation process described here could help hospitals improve efficient product selection and purchasing decisions for intravenous cannulae.
PMCID: PMC3882495  PMID: 24364899
Intravenous cannula; Purchasing guide
19.  Procalcitonin as a marker of sepsis and outcome in patients with neurotrauma: an observation study 
BMC Anesthesiology  2013;13:48.
Procalcitonin (PCT) is a reliable biomarker of sepsis and infection. The level of PCT associated with sepsis and infection in patients with traumatic brain injury is currently unknown. The purpose of this study was to investigate the value of PCT and C-reactive protein (CRP) as diagnostic markers of sepsis and to evaluate the prognostic value of these markers related to the severity of injury, sepsis and mortality.
105 adult patients with neurotrauma were enrolled in this study from June 2011 to February 2013. PCT and CRP were measured at admission and 2, 3, 5 and 7 days after admission. The sepsis criteria established by American College of Chest Physicians /Society of Critical Care Medicine Consensus Conference were used to identify patients. Injury Severity Score (ISS) and Glasgow Coma Score (GCS) were used to assess the severity of the injury. All these patients were monitored for 28 days.
At admission, the median level of PCT was consistent with the severity of brain injury as follows: mild 0.08 ng/ml (0.05 - 0.13), moderate 0.25 ng/ml (0.11 - 0.55) and severe 0.31 ng/ml (0.17 - 0.79), but the range of CRP levels varied greatly within the given severity of brain injury. Seventy-one (67.6%) patients developed sepsis. The initial levels of PCT at admission were statistically higher in patients with sepsis, compared with patients with systemic inflammatory response syndrome (SIRS), but there were no differences in the initial concentration of CRP between sepsis and SIRS. After adjusting for these parameters, multivariate logistic regression analysis revealed that PCT was an independent risk factor for septic complications (p < 0.05). The areas under the ROCs at admission for the prediction of mortality were 0.76 (p < 0.05) and 0.733 for PCT and CRP, respectively.
Increased levels of PCT during the course of the ICU stay could be an important indicator for the early diagnosis of sepsis after neurotrauma. In addition, high serum levels of PCT in patients with neurotrauma at admission indicate an increased risk of septic complications, and the daily measurement of PCT assists in guiding antibiotic therapy in neurotrauma patients.
PMCID: PMC3932500  PMID: 24330775
Procalcitonin; Systemic inflammatory response syndrome (SIRS); Sepsis; Mortality; Traumatic brain injury
20.  Repeated open endotracheal suctioning causes gradual desaturation but does not exacerbate lung injury compared to closed endotracheal suctioning in a rabbit model of ARDS 
BMC Anesthesiology  2013;13:47.
Although endotracheal suctioning induces alveolar derecruitment during mechanical ventilation, it is not clear whether repeated endotracheal suctioning exacerbates lung injuries. The present study aimed to determine whether repeated open endotracheal suctioning (OS) exacerbates lung injury compared to closed endotracheal suctioning (CS) during mechanical ventilation in an animal model of acute respiratory distress syndrome (ARDS).
Briefly, thirty six Japanese white rabbits were initially ventilated in pressure-controlled mode with a constant tidal volume (6 mL/kg). Then, lung injury was induced by repeated saline lavage. The rabbits were divided into four groups, namely: a) OS; b) CS; c) control with ARDS only; d) and healthy control (HC) without ARDS. Animals in all the groups were then ventilated with positive end expiratory pressure (PEEP) at 10 cm H2O. CS was performed using 6 French-closed suctioning catheters connected to endotracheal tube under the following conditions: a) a suctioning time and pressure of 10 sec and 140 mm Hg, respectively; and b) a suction depth of 2 cm (length of adapter) plus tracheal tube. OS was performed using the same conditions described for CS, except the ventilator was disconnected from the animals. Each endotracheal suctioning was performed at an interval of 30 min.
PaO2/FIO2 (P/F) ratio for CS, control and HC groups remained at >400 for 6 hours, whereas that of the OS group progressively declined to 300 (p < 0.05), with each suctioning. However, no difference was observed either in lung injury score (histology) or in the expression pattern of inflammatory cytokines (tumor necrosis factor-α and interleukin-6) after 6 hours between the OS and CS groups in the circulatory as well as the pulmonary tissues.
Progressive arterial desaturation under conditions of repeated endotracheal suctioning is greater in OS than in CS time-dependently. However, OS does not exacerbate lung injury during mechanical ventilation when observed over a longer time span (6 hours) of repeated endotracheal suctioning, based on morphological and molecular analysis.
PMCID: PMC3878988  PMID: 24308643
Acute respiratory distress syndrome; Lung injury; Repeated endotracheal suctioning; Repeated derecruitments; Mechanical ventilation
21.  Comparison of intraoperative blood loss during spinal surgery using either remifentanil or fentanyl as an adjuvant to general anesthesia 
BMC Anesthesiology  2013;13:46.
Remifentanil enhances intraoperative hemodynamic stability, suggesting that it may decrease intraoperative blood loss when included as an adjuvant to general anesthesia. This retrospective study compared intraoperative blood loss during spinal surgery in patients administered either remifentanil or fentanyl as an opioid adjuvant.
We reviewed clinical and surgical data from 64 consecutive laminoplasty or laminectomy patients treated at National Hospital Organization Zentsuji Hospital between April 2010 and March 2011. Patients received either remifentanil (n = 35) or fentanyl (n = 29) as an opioid analgesic during general anesthesia. In addition to intraoperative blood loss, indices of hemodynamic stability, including heart rate as well as systolic, mean, and diastolic blood pressure (BP), were compared over the entire perioperative period between remifentanil and fentanyl groups.
The remifentanil group exhibited significantly lower intraoperative arterial BP than the fentanyl group. Intraoperative blood loss was also significantly lower in the remifentanil group (125 ± 67 mL vs. 165 ± 82 mL, P = 0.035).
Intraoperative blood loss during spinal surgery was decreased in patients who received remifentanil as an opioid adjuvant, possibly because of lower intraoperative BP. A larger-scale prospective randomized controlled trial is warranted to confirm our results and to test whether remifentanil can decrease intraoperative blood loss during other surgical procedures.
PMCID: PMC3880217  PMID: 24304964
Intraoperative blood loss; Remifentanil; Hemodynamics; Fentanyl; Spinal surgery; General anesthesia
22.  Prolonged non-survival in PICU: does a do-not-attempt-resuscitation order matter 
BMC Anesthesiology  2013;13:43.
Etiologies of pediatric intensive care unit (PICU) mortality are diverse. This study aimed to investigate the pattern of PICU mortality in a regional trauma center, and explore factors associated with prolonged non-survival.
Demographic data of all PICU deaths in a regional trauma center were analyzed. Factors associated with prolonged nonsurvival (length of stay) were investigated with univariate log rank and multivariate Cox-Regression forward stepwise tests.
There were 88 deaths (males 61%; infants 23%) over 10 years (median PICU stay = 3.5 days, interquartile range: 1 and 11 days). The mean annual mortality rate of PICU admissions was 5.8%. Septicemia with gram positive, gram negative and fungal pathogens were present in 13 (16%), 13 (16%) and 4 (5%) of these patients, respectively. Viruses were isolated in 25 patients (28%). Ninety percent of these 88 patients were ventilated, 75% required inotropes, 92% received broad spectrum antibiotic coverage, 32% received systemic corticosteroids, 56% required blood transfusion and 39% received anticonvulsants. Thirty nine patients (44%) had a DNAR (Do-Not-Attempt-Resuscitation) order with their deaths at the PICU. Comparing with non-trauma category, trauma patients had higher mortality score, no premorbid disease, suffered asystole preceding PICU admission and subsequent brain death. Oncologic conditions were the most prevalent diagnosis in the non-trauma category. There was no gunshot or asthma death in this series. Prolonged non-survival was significantly associated with DNAR, fungal infections, and mechanical ventilation but negatively associated with bacteremia.
Death in the PICU is a heterogeneous event that involves infants and children. Resuscitation was not attempted at the time of their deaths in nearly half of the patients in honor of parents’ wishes. Parents often make DNAR decision when medical futility becomes evident. They could be reassured that DNAR did not mean “abandoning” care. Instead, DNAR patients had prolonged PICU stay and received the same level of PICU supports as patients who did not respond to cardiopulmonary resuscitation.
PMCID: PMC3840561  PMID: 24237685
Bacteria; Fungus; PICU; Pediatric intensive care; Malignancy; Mortality; Oncology; PIM2; Sepsis; Trauma; Virus; Do-not-attempt-resuscitation (DNAR); Not-responding-to-cardiopulmonary-resuscitation (NRCPR); Brain death; Organ donation
23.  Perioperative blood transfusions and survival in patients with non-small cell lung cancer: a retrospective study 
BMC Anesthesiology  2013;13:42.
Perioperative blood transfusions have been associated with poor clinical outcomes in the context of oncological surgery. Current literature is inconclusive whether blood transfusions are linked to shorter recurrence free and overall survival after lung cancer surgery. We hypothesize that blood transfusions in patients undergoing surgery for non-small cell lung cancer are associated with poor oncological survival.
After IRB approval, perioperative data from 636 patients who underwent lung cancer surgery was collected. Patients were evaluated for time to tumor recurrence and overall survival.
60 patients were transfused and 576 subjects were not. Patients who received transfusion were more likely to have more advanced disease (p = 0.018), and preoperative low hemoglobin concentrations (p < 0.0001) compared to non-transfused patients. In the multivariable Cox regression analysis, blood transfusion was associated with a significant reduction in recurrence free survival (p = 0.025), HR: 1.55 (95% CI: 1.06-2.27) and overall survival (p = 0.0002) HR: 2.04 (95% CI: 1.41-2.97). However, analysis after propensity score matching between the two groups revealed that the effect of blood transfusion was significant for reduction in overall survival (p = 0.0356), HR: 1.838 (95% CI: 1.04-3.22) but not for recurrence free survival (p = 0.1460), HR: 1.493 (95% CI: 0.87-2.56).
Perioperative administration of red blood cells appears be associated with a decreased overall survival but not recurrence free survival after lung cancer surgery. Our study has the limitations of a retrospective review. Hence, our results should be confirmed by a prospective randomized control trial.
PMCID: PMC3832885  PMID: 24228905
24.  Non-invasive detection of hypovolemia or fluid responsiveness in spontaneously breathing subjects 
BMC Anesthesiology  2013;13:40.
In the assessment of hypovolemia the value of functional hemodynamic monitoring during spontaneous breathing is debated. The aim of our study was to investigate in spontaneously breathing subjects the changes in hemodynamic parameters during graded central hypovolemia and to test whether slow patterned breathing improved the discriminative value of stroke volume (SV), pulse pressure (PP), and their variations (SVV, PPV). In addition, we tested the alterations in labial microcirculation.
20 healthy volunteers participated in our study. Central hypovolemia was induced by lower body negative pressure (LBNP). Continuous signals of ECG, non-invasive blood pressure and central venous pressure were recorded. During baseline and each stage of LBNP the labial microcirculation was investigated by orthogonal polarization spectral imaging, 3 minute periods of patterned breathing at 6 and 15/min respiratory rate were performed, and central venous blood gas analysis was done. Data from baseline and those of different LBNP levels were compared by analysis of variance and those of different breathing rates by t-test. Finally, we performed ROC analysis to assess the discriminative values of SV, PP, SVV and PPV.
Moderate central hypovolemia induced by LBNP caused significant, clinically relevant falls in PP (p < 0.05) and SV and central venous oxygen saturation (ScvO2) (p < 0.001). The proportion of perfused vessels (p < 0.001) and microvascular flow index decreased (p < 0.05). PPV increased (p < 0.001), however the magnitude of fluctuations was greater during slow patterned breathing (p < 0.001). SVV increased only during slow patterned breathing (p < 0.001). ROC analysis confirmed the best predictive value for SV (at 56 ml cut-off AUC 0.97, sensitivity 94%, specificity 95%). Slow patterned breathing improved the discriminative value of SVV (p = 0.0023).
Functional hemodynamic monitoring with slow patterned breathing to control spontaneous respiration may be worthy for further study in different populations for the assessment of hypovolemia and the prediction of volume responsiveness.
PMCID: PMC3829671  PMID: 24188480
Hypovolemia; Functional hemodynamic monitoring; Spontaneous breathing; Microcirculation
25.  Burnout in intensive care units - a consideration of the possible prevalence and frequency of new risk factors: a descriptive correlational multicentre study 
BMC Anesthesiology  2013;13:38.
The provision of Intensive Care (IC) can lead to a health care provider’s physical, psychological and emotional exhaustion, which may develop into burnout. We notice the absence of specific studies regarding this syndrome in Portuguese Intensive Care Units (ICUs). Our main objective is to study the incidence and risk factors of burnout in Portuguese ICUs.
A self-fulfilment questionnaire containing 3 items: (i) socio-demographic data of the study population; (ii) experiences in the workplace; (iii) Maslach Burnout Inventory (MBI) - was applied to evaluate the influence of distinct factors on the prevalence of burnout among physicians and nurses working in ICUs.
Three hundred professionals (82 physicians and 218 nurses) from ten ICUs were included in the study, out of a total of 445 who were eligible. There was a high rate of burnout among professionals working in Portuguese ICUs, with 31% having a high level of burnout. However, when burnout levels among nurses and physicians were compared, no significant difference was found. Using multivariate analysis, we identified gender as being a risk factor, where female status increases the risk of burnout. In addition, higher levels of burnout were associated with conflicts and ethical decision making regarding withdrawing treatments. Having a temporary work contract was also identified as a risk factor. Conversely, working for another service of the same health care institution acts as a protective factor.
A high rate of burnout was identified among professionals working in Portuguese ICUs. This study highlights some new risk factors for burnout (ethical decision making, temporary work contracts), and also protective ones (maintaining activity in other settings outside the ICU) that were not previously reported. Preventive and interventive programmes to avoid and reduce burnout syndrome are of paramount importance in the future organization of ICUs and should take the above results into account.
PMCID: PMC3826848  PMID: 24172172
Burnout; Intensive Care; Risk factors

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