Entropy and bispectral index for assessment of sedation, analgesia and the effects of unpleasant stimuli in critically ill patients: an observational study

INTRODUCTION: Sedative and analgesic drugs are frequently used in critically ill patients. Their overuse may prolong mechanical ventilation and length of stay in the intensive care unit. Guidelines recommend use of sedation protocols that include sedation scores and trials of sedation cessation to minimize drug use. We evaluated processed electroencephalography (response and state entropy and bispectral index) as an adjunct to monitoring effects of commonly used sedative and analgesic drugs and intratracheal suctioning. METHODS: Electrodes for monitoring bispectral index and entropy were placed on the foreheads of 44 critically ill patients requiring mechanical ventilation and who previously had no brain dysfunction. Sedation was targeted individually using the Ramsay Sedation Scale, recorded every 2 hours or more frequently. Use of and indications for sedative and analgesic drugs and intratracheal suctioning were recorded manually and using a camera. At the end of the study, processed electroencephalographical and haemodynamic variables collected before and after each drug application and tracheal suctioning were analyzed. Ramsay score was used for comparison with processed electroencephalography when assessed within 15 minutes of an intervention. RESULTS: The indications for boli of sedative drugs exhibited statistically significant, albeit clinically irrelevant, differences in terms of their association with processed electroencephalographical parameters. Electroencephalographical variables decreased significantly after bolus, but a specific pattern in electroencephalographical variables before drug administration was not identified. The same was true for opiate administration. At both 30 minutes and 2 minutes before intratracheal suctioning, there was no difference in electroencephalographical or clinical signs in patients who had or had not received drugs 10 minutes before suctioning. Among patients who received drugs, electroencephalographical parameters returned to baseline more rapidly. In those cases in which Ramsay score was assessed before the event, processed electroencephalography exhibited high variation. CONCLUSIONS: Unpleasant or painful stimuli and sedative and analgesic drugs are associated with significant changes in processed electroencephalographical parameters. However, clinical indications for drug administration were not reflected by these electroencephalographical parameters, and barely by sedation level before drug administration or tracheal suction. This precludes incorporation of entropy and bispectral index as target variables for sedation and analgesia protocols in critically ill patients.

Preemptive carprofen for peri-operative analgesia in dogs undergoing Tibial Plateau Leveling Osteotomy (TPLO): a prospective, randomized, blinded, placebo controlled clinical trial

Eighteen client-owned dogs undergoing Tibial Plateau Leveling Osteotomy (TPLO) were included in this blinded clinical study and randomly assigned to one of two treatment groups. Group C (carprofen) received intravenous (IV) carprofen, 4 mg/kg, prior to anesthesia, whereas group P (placebo) received IV saline. General anesthesia was maintained with isoflurane in oxygen and a constant rate infusion (CRI) of sufentanyl IV. Intra-operatively, assessment of nociception was based on changes in physiological parameters and on the analgesics requirement, whereas in the post-operative period evaluation of pain was performed by using a Hellyer and Gaynor pain score and by comparing the doses of rescue buprenorphine required by the two treatment groups. Although no statistically significant differences in intra-operative sufentanyl doses were found between treatment groups, group C had superior cardiovascular stability, and lower post-operative pain scores and rescue buprenorphine doses than group P. Our results indicate that administration of carprofen prior to surgery was effective in improving peri-operative analgesia in dogs undergoing TPLO.

Clinical and pathological analysis of epidural inflammation in intervertebral disk extrusion in dogs

BACKGROUND Little is known about the pathologic changes in the epidural space after intervertebral disk (IVD) extrusion in the dog. OBJECTIVES To analyze the pathology of the epidural inflammatory response, and to search for correlations between this process and clinical findings. METHODS Clinical data from 105 chondrodystrophic (CD) and nonchondrodystrophic (NCD) dogs with IVD extrusion were recorded. Epidural material from these dogs was examined histopathologically and immunohistochemically. Using statistical analysis, we searched for correlations between severity of epidural inflammation and various clinical and pathologic variables. RESULTS Most dogs exhibited an epidural inflammatory response, ranging from acute invasion of neutrophils to formation of chronic granulation tissue. The mononuclear inflammatory infiltrates consisted mostly of monocytes and macrophages and only few T and B cells. Surprisingly, chronic inflammatory patterns also were found in animals with an acute clinical history. Severity of the epidural inflammation correlated with degree of the epidural hemorrhage and nucleus pulposus calcification (P = .003 and .040), but not with age, chondrodystrophic phenotype, neurologic grade, back pain, pretreatment, or duration. The degree of inflammation was statistically (P = .021) inversely correlated with the ability to regain ambulation. CONCLUSION AND CLINICAL IMPORTANCE Epidural inflammation occurs in the majority of dogs with IVD extrusion and may develop long before the onset of clinical signs. Presence of calcified IVD material and hemorrhage in the epidural space may be the triggers of this lesion rather than an adaptive immune response to the nucleus pulposus as suggested in previous studies. Because epidural inflammation may affect outcome, further research is warranted.

Atlantoaxial epidural abscess secondary to grass awn migration in a dog.

A two-year-old female Lucerne Hound was presented with a one-week history of signs of progressive neck pain, inappetence, apathy, and an elevated rectal temperature. Findings of magnetic resonance imaging (MRI) were consistent with a foreign body abscess in the epidural space at the level of the first and second cervical vertebrae. A left-sided dorso-lateral atlantoaxial approach was performed, revealing an epidural abscess containing a grass awn. The clinical signs resolved within three days of surgery and the dog made a full recovery. This case report shows that grass awns can migrate to the atlantoaxial region in dogs and MRI findings lead to a suspicion of caudo-cranial migration within the spinal canal.

Limitations of the use of pressure waves to verify correct epidural needle position in dogs

The use of pressure waves to confirm the correct position of the epidural needle has been described in several domestic species and proposed as a valid alternative to standard methods, namely, control radiographic exam and fluoroscopy. The object of this retrospective clinical study was to evaluate the sensitivity of the epidural pressure waves as a test to verify the correct needle placement in the epidural space in dogs, in order to determine whether this technique could be useful not only in the clinical setting but also when certain knowledge of needle's tip position is required, for instance when performing clinical research focusing on epidural anaesthesia. Of the 54 client-owned dogs undergoing elective surgeries and enrolled in this retrospective study, only 45% showed epidural pressure waves before and after epidural injection. Twenty-six percent of the animals showed epidural pressure waves only after the injection, whereas 29% of the dogs showed epidural pressure waves neither before nor after injection and were defined as false negatives. Our results show that the epidural pressure wave technique to verify epidural needle position lacks sensitivity, resulting in many false negatives. As a consequence, the applicability of this technique is limited to situations in which precise, exact knowledge of the needle's tip position is not mandatory.

Increased intraoperative epidural pressure in lumbar spinal stenosis patients with a positive nerve root sedimentation sign

Purpose The sedimentation sign (SedSign) has been shown to discriminate well between selected patients with and without lumbar spinal stenosis (LSS). The purpose of this study was to compare the pressure values associated with LSS versus non-LSS and discuss whether a positive SedSign may be related to increased epidural pressure at the level of the stenosis. Methods We measured the intraoperative epidural pressure in five patients without LSS and a negative SedSign, and in five patients with LSS and a positive SedSign using a Codman TM catheter in prone position under radioscopy. Results Patients with a negative SedSign had a median epidural pressure of 9 mmHg independent of the measurement location. Breath and pulse-synchronous waves accounted for 1–3 mmHg. In patients with monosegmental LSS and a positive SedSign, the epidural pressure above and below the stenosis was similar (median 8–9 mmHg). At the level of the stenosis the median epidural pressure was 22 mmHg. A breath and pulse-synchronous wave was present cranial to the stenosis, but absent below. These findings were independent of the cross-sectional area of the spinal canal at the level of the stenosis. Conclusions Patients with LSS have an increased epidural pressure at the level of the stenosis and altered pressure wave characteristics below. We argue that the absence of sedimentation of lumbar nerve roots to the dorsal part of the dural sac in supine position may be due to tethering of affected nerve roots at the level of the stenosis.

Dominance of chemokine ligand 2 and matrix metalloproteinase-2 and -9 and suppression of pro-inflammatory cytokines in the epidural compartment after intervertebral disc extrusion in a canine model

BACKGROUND CONTEXT In canine intervertebral disc (IVD) disease, a useful animal model, only little is known about the inflammatory response in the epidural space. PURPOSE To determine messenger RNA (mRNA) expressions of selected cytokines, chemokines, and matrix metalloproteinases (MMPs) qualitatively and semiquantitatively over the course of the disease and to correlate results to neurologic status and outcome. STUDY DESIGN/SETTING Prospective study using extruded IVD material of dogs with thoracolumbar IVD extrusion. PATIENT SAMPLE Seventy affected and 13 control (24 samples) dogs. OUTCOME MEASURES Duration of neurologic signs, pretreatment, neurologic grade, severity of pain, and outcome were recorded. After diagnostic imaging, decompressive surgery was performed. METHODS Messenger RNA expressions of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF), interferon (IFN)γ, MMP-2, MMP-9, chemokine ligand (CCL)2, CCL3, and three housekeeping genes was determined in the collected epidural material by Panomics 2.0 QuantiGene Plex technology. Relative mRNA expression and fold changes were calculated. Relative mRNA expression was correlated statistically to clinical parameters. RESULTS Fold changes of TNF, IL-1β, IL-2, IL-4, IL-6, IL-10, IFNγ, and CCL3 were clearly downregulated in all stages of the disease. MMP-9 was downregulated in the acute stage and upregulated in the subacute and chronic phase. Interleukin-8 was upregulated in acute cases. MMP-2 showed mild and CCL2 strong upregulation over the whole course of the disease. In dogs with severe pain, CCL3 and IFNγ were significantly higher compared with dogs without pain (p=.017/.020). Dogs pretreated with nonsteroidal anti-inflammatory drugs revealed significantly lower mRNA expression of IL-8 (p=.017). CONCLUSIONS The high CCL2 levels and upregulated MMPs combined with downregulated T-cell cytokines and suppressed pro-inflammatory genes in extruded canine disc material indicate that the epidural reaction is dominated by infiltrating monocytes differentiating into macrophages with tissue remodeling functions. These results will help to understand the pathogenic processes representing the basis for novel therapeutic approaches. The canine IVD disease model will be rewarding in this process.

Attitudes of Swiss veterinarians towards pain and analgesia in dogs and cats.

A survey was performed to evaluate the use of perioperative analgesia in dogs and cats by veterinary practitioners. Questions were grouped in seven sections recording personal data, education in veterinary analgesia, general ideology regarding treatment of perioperative pain, personal experience, assessment, and use of main analgesics to treat perioperative pain. A total of 258 received forms were analyzed. Based on 5 questions, 88 % showed excellent motivation to use perioperative pain therapy. The main reason declared for the use of analgesics was to relieve the patient from pain (64.1 %). Most veterinarians reported to routinely administer analgesics before (71 - 96 %) or after (2 - 23 %) surgery. The most used analgesics were non-steroidal anti-inflammatory drugs (carprofen, meloxicam) and opioids (butorphanol, buprenorphine). Animals were routinely evaluated for pain after recovery. Only 43.8 % of veterinarians declared to use loco-regional anaesthesia. Swiss veterinarians appear to recognize well the need for perioperative pain treatment. However, weakness was shown in evaluating pain severity, distinguishing between opioid classes, and using loco-regional anaesthesia.

Diffusion of contrast medium after four different techniques for analgesia of the proximal metacarpal region: an in vivo and in vitro study

REASONS FOR PERFORMING STUDY: There is limited information on potential diffusion of local anaesthetic solution after various diagnostic analgesic techniques of the proximal metacarpal region. OBJECTIVE: To document potential distribution of local anaesthetic solution following 4 techniques used for diagnostic analgesia of the proximal metacarpal region. METHODS: Radiodense contrast medium was injected around the lateral palmar or medial and lateral palmar metacarpal nerves in 8 mature horses, using 4 different techniques. Radiographs were obtained 0, 10 and 20 min after injection and were analysed subjectively. A mixture of radiodense contrast medium and methylene blue was injected into 4 cadaver limbs; the location of the contrast medium and dye was determined by radiography and dissection. RESULTS: Following perineural injection of the palmar metacarpal nerves, most of the contrast medium was distributed in an elongated pattern axial to the second and fourth metacarpal bones. The carpometacarpal joint was inadvertently penetrated in 4/8 limbs after injections of the palmar metacarpal nerves from medial and lateral approaches, and in 1/8 limbs when both injections were performed from the lateral approach. Following perineural injection of the lateral palmar nerve using a lateral approach, the contrast medium was diffusely distributed in all but one limb, in which the carpal sheath was inadvertently penetrated. In 5/8 limbs, following perineural injection of the lateral palmar nerve using a medial approach, the contrast medium diffused proximally to the distal third of the antebrachium. CONCLUSIONS AND POTENTIAL RELEVANCE: Inadvertent penetration of the carpometacarpal joint is common after perineural injection of the palmar metacarpal nerves, but less so if both palmar metacarpal nerves are injected using a lateral approach. Following injection of the lateral palmar nerve using a medial approach, the entire palmar aspect of the carpus may be desensitised.

Paracetamol for perioperative analgesia. Old substance - new insights

Since paracetamol was first synthesized in 1878 it has become one of the most popular and widely used drugs for the first-line treatment of fever and pain. The reasons for this popularity are a wide variety of formulations, an assumed positive safety record and the wide availability as an over-the-counter drug. However, recently several studies questioned the positive risk-benefit ratio of paracetamol for postoperative pain by observing several possible adverse effects and limitations. The aim of the present review is to give an update of the recent literature on the efficacy of paracetamol for postoperative pain and on the value of the clinical relevance of different adverse effects of paracetamol. Finally, based on the current findings the authors try to assess the role of paracetamol for the treatment of postoperative pain.

Addition of magnesium sulphate to ropivacaine for spinal analgesia in dogs undergoing tibial plateau levelling osteotomy

The aim of this blinded, randomised, prospective clinical trial was to determine whether the addition of magnesium sulphate to spinally-administered ropivacaine would improve peri-operative analgesia without impairing motor function in dogs undergoing orthopaedic surgery. Twenty client-owned dogs undergoing tibial plateau levelling osteotomy were randomly assigned to one of two treatment groups: group C (control, receiving hyperbaric ropivacaine by the spinal route) or group M (magnesium, receiving a hyperbaric combination of magnesium sulphate and ropivacaine by the spinal route). During surgery, changes in physiological variables above baseline were used to evaluate nociception. Arterial blood was collected before and after spinal injection, at four time points, to monitor plasma magnesium concentrations. Post-operatively, pain was assessed with a modified Sammarco pain score, a Glasgow pain scale and a visual analogue scale, while motor function was evaluated with a modified Tarlov scale. Assessments were performed at recovery and 1, 2 and 3 h thereafter. Fentanyl and buprenorphine were administered as rescue analgesics in the intra- and post-operative periods, respectively. Plasma magnesium concentrations did not increase after spinal injection compared to baseline. Group M required less intra-operative fentanyl, had lower Glasgow pain scores and experienced analgesia of longer duration than group C (527.0 ± 341.0 min vs. 176.0 ± 109.0 min). However, in group M the motor block was significantly longer, which limits the usefulness of magnesium for spinal analgesia at the investigated dose. Further research is needed to determine a clinically effective dose with shorter duration of motor block for magnesium used as an additive to spinal analgesic agents.

Resistive-Polymer Versus Forced-Air Warming: Comparable Efficacy in Orthopedic Patients

BACKGROUND: Several adverse consequences are caused by mild perioperative hypothermia. Maintaining normothermia with patient warming systems, today mostly with forced air (FA), has thus become a standard procedure during anesthesia. Recently, a polymer-based resistive patient warming system was developed. We compared the efficacy of a widely distributed FA system with the resistive-polymer (RP) system in a prospective, randomized clinical study. METHODS: Eighty patients scheduled for orthopedic surgery were randomized to either FA warming (Bair Hugger warming blanket #522 and blower #750, Arizant, Eden Prairie, MN) or RP warming (Hot Dog Multi-Position Blanket and Hot Dog controller, Augustine Biomedical, Eden Prairie, MN). Core temperature, skin temperature (head, upper and lower arm, chest, abdomen, back, thigh, and calf), and room temperature (general and near the patient) were recorded continuously. RESULTS: After an initial decrease, core temperatures increased in both groups at comparable rates (FA: 0.33 degrees C/h +/- 0.34 degrees C/h; RP: 0.29 degrees C/h +/- 0.35 degrees C/h; P = 0.6). There was also no difference in the course of mean skin and mean body (core) temperature. FA warming increased the environment close to the patient (the workplace of anesthesiologists and surgeons) more than RP warming (24.4 degrees C +/- 5.2 degrees C for FA vs 22.6 degrees C +/- 1.9 degrees C for RP at 30 minutes; P(AUC) <0.01). CONCLUSION: RP warming performed as efficiently as FA warming in patients undergoing orthopedic surgery.

Blockade of the sinuvertebral nerve for the diagnosis of lumbar diskogenic pain: an exploratory study

In this exploratory study we evaluated sensitivity and target specificity of sinuvertebral nerve block (SVNB) for the diagnosis of lumbar diskogenic pain. Diskography has been the diagnostic gold standard. Fifteen patients with positive diskography underwent SVNB via interlaminar approach to the posterior aspect of the disk. Success was defined as > or = 80% pain reduction or excellent relief of physical restrictions after the block. The sensitivity was 73.3% (95% CI: 50.9%-95.7%). The target specificity was 40% (15.2%-64.8%). The results indicate that SVNB cannot yet replace diskography but encourage future studies to improve its target specificity.

What does local tenderness say about the origin of pain? An investigation of cervical zygapophysial joint pain

BACKGROUND: Mechanical pain sensitivity is assessed in every patient with pain, either by palpation or by quantitative pressure algometry. Despite widespread use, no studies have formally addressed the usefulness of this practice for the identification of the source of pain. We tested the hypothesis that assessing mechanical pain sensitivity distinguishes damaged from healthy cervical zygapophysial (facet) joints. METHODS: Thirty-three patients with chronic unilateral neck pain were studied. Pressure pain thresholds (PPTs) were assessed bilaterally at all cervical zygapophysial joints. The diagnosis of zygapophysial joint pain was made by selective nerve blocks. Primary analysis was the comparison of the PPT between symptomatic and contralateral asymptomatic joints. The secondary end points were as follows: differences in PPT between affected and asymptomatic joints of the same side of patients with zygapophysial joint pain; differences in PPT at the painful side between patients with and without zygapophysial joint pain; and sensitivity and specificity of PPT for 2 different cutoffs (difference in PPT between affected and contralateral side by 1 and 30 kPa, meaning that the test was considered positive if the difference in PPT between painful and contralateral side was negative by at least 1 and 30 kPa, respectively). The PPT of patients was also compared with the PPT of 12 pain-free subjects. RESULTS: Zygapophysial joint pain was present in 14 patients. In these cases, the difference in mean PPT between affected and contralateral side (primary analysis) was −6.2 kPa (95% confidence interval: −19.5 to 7.2, P = 0.34). In addition, the secondary analyses yielded no statistically significant differences. For the cutoff of 1 kPa, sensitivity and specificity of PPT were 67% and 16%, respectively, resulting in a positive likelihood ratio of 0.79 and a diagnostic confidence of 38%. When the cutoff of 30 kPa was considered, the sensitivity decreased to only 13%, whereas the specificity increased to 95%, resulting in a positive likelihood ratio of 2.53 and a diagnostic confidence of 67%. The PPT was significantly lower in patients than in pain-free subjects (P < 0.001). CONCLUSIONS: Assessing mechanical pain sensitivity is not diagnostic for cervical zygapophysial joint pain. The finding should stimulate further research into a diagnostic tool that is widely used in the clinical examination of patients with pain.

Ventilation-perfusion ratio in perflubron during partial liquid ventilation

BACKGROUND: Functional magnetic resonance imaging (fMRI) of fluorine-19 allows for the mapping of oxygen partial pressure within perfluorocarbons in the alveolar space (Pao(2)). Theoretically, fMRI-detected Pao(2) can be combined with the Fick principle approach, i.e., a mass balance of oxygen uptake by ventilation and delivery by perfusion, to quantify the ventilation-perfusion ratio (Va/Q) of a lung region: The mixed venous blood and the inspiratory oxygen fraction, which are equal for all lung regions, are measured. In addition, the local expiratory oxygen fraction and the end capillary oxygen content, both of which may differ between the lung regions, are calculated using the fMRI-detected Pao(2). We investigated this approach by numerical simulations and applied it to quantify local Va/Q in the perfluorocarbons during partial liquid ventilation. METHODS: Numerical simulations were performed to analyze the sensitivity of the Va/Q calculation and to compare this approach with another one proposed by Rizi et al. in 2004 (Magn Reson Med 2004;52:65-72). Experimentally, the method was used during partial liquid ventilation in 7 anesthetized pigs. The Pao(2) distribution in intraalveolar perflubron was measured by fluorine-19 MRI. Respiratory gas fractions together with arterial and mixed venous blood samples were taken to quantify oxygen partial pressure and content. Using the Fick principle, the local Va/Q was estimated. The impact of gravity (nondependent versus dependent) of perflubron dose (10 vs 20 mL/kg body weight) and of inspired oxygen fraction (Fio(2)) (0.4-1.0) on Va/Q was examined. RESULTS: In numerical simulations, the Fick principle proved to be appropriate over the Va/Q range from 0.02 to 2.5. Va/Q values were in acceptable agreement with the method published by Rizi et al. In the experimental setting, low mean Va/Q values were found in perflubron (confidence interval [CI] 0.08-0.29 with 20 mL/kg perflubron). At this dose, Va/Q in the nondependent lung was higher (CI 0.18-0.39) than in the dependent lung regions (CI 0.06-0.16; P = 0.006; Student t test). Differences depending on Fio(2) or perflubron dose were, however, small. CONCLUSION: The results show that derivation of Va/Q from local Po(2) measurements using fMRI in perflubron is feasible. The low detected Va/Q suggests that oxygen transport into the perflubron-filled alveolar space is significantly restrained.