Systematic evaluation of the highest current threshold for regional anaesthesia in a porcine model

Background: The purpose of this study was to determine systematically the highest minimal stimulation current threshold for regional anaesthesia in pigs. Methods: In an established pig model for regional anaesthesia, needle placements applying electric nerve stimulation were performed. The primary outcome was the frequency of close needle to nerve placements as assessed by resin injectates and subsequent anatomical evaluation. Following a statistical model (continual reassessment method), the applied output currents were selected to limit the necessary number of punctures, while providing guidance towards the highest output current range. Results: Altogether 186 punctures were performed in 11 pigs. Within the range of 0.3–1.4 mA, no distant needle to nerve placement was found. In the range of 1.5–4.1 mA, 43 distant needle to nerve placements occurred. The range of 1.2–1.4 mA was the highest interval that resulted in a close needle to nerve placement rate of ≥95%. Conclusions: In the range of 0.3–1.4 mA, all resin deposition was found to be adjacent to nerve epineurium. The application of minimal current intensities up to 1.4 mA does not obviously lead to a reduction of epineural injectate contacts in pigs. These findings suggest that stimulation current thresholds up to 1.4 mA result in equivalent needle tip localisation in pigs.     

Splenectomy does not influence outcome of pneumococcal septicemia in a porcine model

The existence of the overwhelming postsplenectomy infection syndrome in adults after traumatic splenectomy is controversial. Due to the similarity of the porcine immune system to man we chose the pig to study subsets of peripheral mononuclear cells after splenectomy and resistance to experimental Pneumococcal infection after splenic surgery and specific immunization. Female miniature pigs were assigned to four operative groups: sham operation, splenectomy, splenic resection, and heterotopic splenic autotransplantation. Hematologic and flow cytometric analysis of mononuclear cells and their subsets revealed a marked leukocytosis following splenectomy and autotransplantation but no significant shift in monocyte and B-cell numbers. Response of leukocytes to septicemia, bacterial elimination from peripheral blood, and mortality were not affected by splenectomy or spleen-preserving operations. Mortality of splenectomized animals was 18%, compared to 42% in sham-operated controls (difference not significant). Immunization protected animals from development of leukopenia, and led to an enhanced bacterial elimination, and a significantly decreased mortality of 5%, compared to 48% in nonimmune animals. Thus our data do not show significant effects of splenectomy on subsets of porcine mononuclear cells or on resistance to experimental Pneumococcal septicemia.     

High thoracic epidural anesthesia does not inhibit sympathetic nerve activity in the lower extremities.

BACKGROUND: Sympathetic nerve activity was recorded in the leg during high thoracic epidural anesthesia with a segmental sensory blockade of the upper thoracic dermatomes to test the hypothesis that the sympathetic blockade accompanying thoracic epidural anesthesia includes caudal parts of the sympathetic nervous system. METHODS: Experiments were performed on 10 patients scheduled for thoracotomy. An epidural catheter was inserted at the T3-T4 or T4-T5 interspace. In the main protocol (seven patients), blood pressure, heart rate, and skin temperature (big toe, thumb) were continuously monitored, and multiunit postganglionic sympathetic nerve activity was recorded with a tungsten microelectrode in a muscle-innervating fascicle of the peroneal nerve. After baseline data collection, muscle sympathetic nerve activity was recorded for an additional 45-min period after epidural injection of 4-6 ml bupivacaine, 5 mg/ml. In an additional three patients, the effects of thoracic epidural anesthesia on skin-innervating sympathetic nerve activity were qualitatively assessed. RESULTS: Activation of thoracic epidural anesthesia caused no significant changes in peroneal muscle sympathetic nerve activity (n = 7), blood pressure, or heart rate. Skin temperature increased significantly in the hand 15 min after activation of the blockade, from 32.7 +/- 2.4 degrees C to 34.4 +/- 1.5 degrees C (mean +/- SD), whereas no changes were observed in foot temperature. The sensory blockade extended from T1 (C4-T2) to T8 (T6-T11). CONCLUSIONS: A high thoracic epidural anesthesia with adequate sensory blockade of upper thoracic dermatomes may be achieved without blockade of caudal parts of the sympathetic nervous system. This finding differs from that of earlier studies that used indirect methods to evaluate changes in sympathetic nerve activity.     

Estimation of equivalent threshold currents using different pulse widths for the epidural stimulation test in a porcine model

Background

The epidural stimulation test can help detect if a catheter is correctly positioned in the epidural space. Previous studies showed that a current of up to 16 mA was required to elicit a motor response, but few peripheral nerve stimulators can produce a current this high. Manipulating pulse width can produce a positive response at a lower current. To clarify the effects of pulse width on the epidural stimulation test, we performed a single-blinded study in a porcine model to estimate the equivalent current needed at varying pulse widths.

Methods

After obtaining local ethics approval, an 18G insulated Tuohy needle was advanced into the epidural space at the lower lumbar spinal level, and a 20G stimulating epidural catheter was advanced 30 cm cephalad. A gradually increasing electrical current was applied, and a motor response was elicited at pulse widths of 0.1, 0.2, 0.3, 0.5, and 1 msec. This was followed by a 1-2 cm catheter withdrawal, and the process was repeated for a total of 15 locations per pig.

Results

Recorded threshold currents ranged from 0.36-9.5 mA at a pulse width of 0.2 msec. Our results show a linear relationship between threshold current and pulse width.

Conclusions

In situations where different pulse widths are needed, the nomograms presented here may be useful to estimate the equivalent threshold current which is required to elicit a motor response according to previously published criteria for epidural stimulation tests.     

The use of electrical stimulation to monitor epidural needle advancement in a porcine model

Muscle twitches elicited with electrical stimulation (ES) during epidural insertion may indicate epidural needle location. We examined the potential application of ES at 5 mA as a continuous method of monitoring the response to epidural needle advancement in a porcine model. Five 20-kg pigs were used in this study. A needle with a stimulating current of 5 mA was inserted at 20 separate levels in each pig. The needle was advanced until a muscle twitch was observed without loss-of-resistance (LOR). The needle position was then assessed using LOR. At the end of the experiment, an autopsy was performed to assess the spinal cord for injury. A total of 100 needle insertions were performed in the 5 pigs. The threshold current in the epidural space was 3.6 +/- 0.6 mA. In 59 of the needle insertions, LOR was not obtained at the depth at which a muscle twitch was initially observed. However, after advancing these 59 needles another 1-2 mm, LOR was obtained. In the other 41 insertions, LOR was observed without further advancement of the needle. Autopsies indicated there were no dural punctures or spinal cord damage in any of the pigs. These observations suggest that ES can be used to signal that the epidural needle is in or approaching the epidural space. However, the high false positive predictive value (59%) makes it impractical and unreliable to detect the precise entry of a needle into the epidural space in pigs.     

Erythropoietin does not attenuate renal dysfunction or inflammation in a porcine model of endotoxemia

Background: Erythropoietin (EPO) is a multifunctional cytokine with anti‐apoptotic, anti‐inflammatory, and organ protective effects. EPO protects against ischemia–reperfusion injuries, and recent reports suggest that EPO also prevents organ dysfunction in experimental sepsis. The aims of this study were to determine whether EPO prevents endotoxemia‐induced organ dysfunction in a porcine model and to characterize the immunomodulatory and anti‐apoptotic effects of EPO. Methods: Twenty‐eight pigs were randomly assigned to three groups: (1) endotoxemia treated with EPO 5000 IU/kg, (2) endotoxemia treated with placebo, and (3) a sham group anesthetized and submitted to sham operation without treatment. A laparotomy was performed, and a flow probe was placed around the left renal artery, which allowed renal blood flow (RBF) measurements. Endotoxemia was induced by an infusion of lipopolysaccharide. After 2 h, the infusion was reduced to a maintenance dose and the animals were fluid resuscitated. The glomerular filtration rate (GFR), RBF, renal oxygen consumption, and plasma cytokines [interleukin (IL)‐1β, IL‐6, IL‐8, IL‐10, and tumor necrosis factor‐alpha] were analyzed. Renal biopsies were analyzed for cytokine content and apoptosis. Results: Endotoxemia elicited impaired renal function, estimated as GFR, and increased the levels of renal apoptotic cells, with no modifying effect of EPO. Furthermore, EPO had no effect on RBF, renal oxygen consumption, or the systemic hemodynamic response to endotoxemia. EPO did not modify the inflammatory response, measured as changes in cytokine levels in plasma and organs. Conclusion: EPO did not confer renal protection in this fluid‐resuscitated porcine model of endotoxemia, and EPO did not modify the inflammatory response.     

The addition of hydromorphone to epidural fentanyl does not affect analgesia in early labour

PURPOSE: Epidural fentanyl after a lidocaine and epinephrine test dose, provides adequate analgesia and allows for ambulation during early labour. The current study was designed to determine the influence of hydromorphone added to an epidural fentanyl bolus (e.g., whether there is an increase in duration of analgesia). METHODS: Forty-four labouring primigravid women, at less than 5 cm cervical dilation, who requested epidural analgesia were enrolled in this randomized, double-blind study. After a 3 mL test dose of lidocaine with epinephrine, patients received fentanyl 100 microgram (in 10 mL volume). They randomly received the fentanyl with either saline or hydromorphone (300 microgram). After administration of the initial analgesic, pain scores and side effects were recorded for each patient at ten, 20, and 30 min, and every 30 min thereafter, by an observer blinded to the technique used. RESULTS: The patients were taller in the hydromorphone group (P < 0.04). There were no other demographic differences between the two groups. The mean duration prior to re-dose was not significantly different in the group that received hydromorphone (135 +/- 52 min) compared to the control group (145 +/- 46 min). Side effects were similar between the two groups. No patient in either group experienced any detectable motor block. CONCLUSION: In early labouring patients, the addition of hydromorphone (300 microgram) to epidural fentanyl (100 microgram after a lidocaine and epinephrine test dose) neither prolongs the duration of analgesia nor affects the ability to ambulate, and cannot be recommended according to the current study.     

Low dose intrathecal ropivacaine with or without sufentanil provides effective analgesia and does not impair motor strength during labour: a pilot study

PURPOSE: Although ropivacaine has been used to provide spinal anesthesia in the surgical population, its intrathecal administration for labour analgesia has only recently been described. We evaluated the effects of low dose intrathecal ropivacaine with or without sufentanil for labour analgesia. METHODS: Thirty-six term parturients in active labour were randomly assigned to receive 3 mg of intrathecal ropivacaine (group R) or 3 mg ropivacaine with 10 microg of sufentanil (group RS). Patients were evaluated by a blinded observer for hypotension, linear analogue score (VAS 0-100) for labour pain, motor power in the lower limbs, onset of analgesia, sensation to cold and pin prick, duration of analgesia, and neonatal Apgar scores. The following day patients were assessed for satisfaction, headache and neurologic deficit. RESULTS: The mean duration of analgesia in the R group was 41.4 +/- 4.9 min and 95.0 +/- 6.1 min in the RS group (mean +/- SEM, P=0.0001). All subjects had satisfactory analgesia at five minutes, although analgesia from the ropivacaine- sufentanil combination was superior to that provided by ropivacaine alone. Total duration of labour was no different between the groups (R- 306 +/- 34, RS- 384 +/- 44 min, P=0.17). No patient showed evidence of motor block. All patients were satisfied with the labour analgesia. No neurological complications were observed. CONCLUSIONS: Low dose ropivacaine provides effective analgesia during labour via the intrathecal route. It can be mixed with sufentanil in the above-mentioned concentrations to improve both the quality and duration of analgesia. Fetal outcome remains favourable. It may provide minimal or no motor block, to facilitate ambulation.     

Vasopressor response in a porcine model of hypothermic cardiac arrest is improved with active compression-decompression cardiopulmonary resuscitation using the inspiratory impedance threshold valve

During normothermic cardiac arrest, a combination of active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) with the inspiratory threshold valve (ITV) significantly improves vital organ blood flow, but this technique has not been studied during hypothermic cardiac arrest. Accordingly, we evaluated the hemodynamic effects of ACD + ITV CPR before, and after, the administration of vasopressin in a porcine model of hypothermic cardiac arrest. Pigs were surface-cooled until their body core temperature was 26 degrees C. After 10 min of untreated ventricular fibrillation, 14 animals were randomly assigned to either ACD CPR with the ITV (n = 7) or to standard (STD) CPR (n = 7). After 8 min of CPR, all animals received 0.4 U/kg vasopressin IV, and CPR was maintained for an additional 10 min in each group; defibrillation was attempted after 28 min of cardiac arrest, including 18 min of CPR. Before the administration of vasopressin, mean +/- SEM common carotid blood flow was significantly higher in the ACD + ITV group compared with STD CPR (67 +/- 13 versus 26 +/- 5 mL/min, respectively; P < 0.025). After vasopressin was given at minute 8 during CPR, mean +/- SEM coronary perfusion pressure was significantly higher in the ACD + ITV group, but did not increase in the STD group (29 +/- 3 versus 15 +/- 2 mm Hg, and 25 +/- 1 versus 14 +/- 1 mm Hg at minute 12 and 18, respectively; P < 0.001); mean +/- SEM common carotid blood flow remained higher at respective time points (33 +/- 8 versus 10 +/- 3 mL/min, and 31 +/- 7 versus 7 +/- 3 mL/min, respectively; P < 0.01). Without active rewarming, spontaneous circulation was restored and maintained for 1 h in three of seven animals in the ACD + ITV group versus none of seven animals in the STD CPR group (not significant). During hypothermic cardiac arrest, ACD CPR with the ITV improved common carotid blood flow compared with STD CPR alone. Moreover, after the administration of vasopressin, coronary perfusion pressure was significantly higher during ACD + ITV CPR, but not during STD CPR. IMPLICATIONS: New strategies are needed to improve the efficiency of cardiopulmonary resuscitation (CPR) in hypothermic cardiac arrest. Active compression-decompression CPR with the inspiratory threshold valve improved carotid blood flow (and coronary perfusion pressure with vasopressin) compared with standard CPR.     

Tachyphylaxis associated with repeated epidural injections of lidocaine is not related to changes in distribution or the rate of elimination from the epidural space

The relationship between tachyphylaxis (measured as a decrease in the rate of regression of sensory levels of analgesia) during repeated epidural injections of lidocaine and both the distribution of lidocaine within the epidural space (as measured by spread of simultaneous injection of the tracer technetium-99m diethylenetriaminepentaacetate [99mTc-DTPA]) and elimination of lidocaine from the epidural space (as measured by serum concentrations of lidocaine) was investigated in 18 patients undergoing minor surgery during lumbar epidural analgesia. Twelve patients received four injections of 20 mL of 2% lidocaine at 2-hr intervals. Epidural distribution was assessed by injection of 99mTc-DTPA diluted in saline on the preoperative day and diluted in an equal volume of 2% lidocaine on the morning before surgery and again after the fourth injection of lidocaine 6 hr later. The distribution of 99mTc-DTPA in the epidural space was unchanged during the three measurements despite significant tachyphylaxis in both sensory analgesia and motor blockade (11 of 12 patients had sensory analgesia 2 hr after the first injection in contrast to only 3 of 12 patients during the third injection). In another six patients 20 mL of 2% lidocaine were injected three times at 2-hr intervals before surgery, with measurements of serum concentrations of lidocaine after the first and last injections. Despite tachyphylaxis (no patient had sensory analgesia 2 hr after the third injection), there was no difference in the rate of disappearance of lidocaine from the epidural space as assessed by plasma lidocaine concentration curves during the first and third injection (0.5 +/- 0.1 and 0.3 +/- 0.04 microgram.mL-1.min-1, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Reduced platelet concentration does not harm PRP effectiveness for ACL repair in a porcine in vivo model

Enhanced primary repair of the ACL using a collagen scaffold loaded with platelets has been shown to improve the functional healing of suture repair in animal models. In this study, our objectives were to determine if lowering the platelet concentration would reduce the structural properties of the repaired ACL and increase postoperative knee laxity. Eight Yucatan mini‐pigs underwent bilateral suture repair. In one knee, the repair was augmented with a collagen scaffold saturated with platelet‐rich plasma (PRP) containing five times the systemic baseline of platelets (5×) while the contralateral knee had a collagen scaffold saturated with PRP containing three times the systemic baseline of platelets (3×). After 13 weeks of healing, knee joint laxity and the structural properties of the ACL were measured. The 3× platelet concentration resulted in a 24.1% decrease in cellular density of the repair tissue (p < 0.05), but did not significantly decrease the structural properties [3× vs. 5×: 362 N vs. 291 N (p = 0.242) and 70 N/mm vs. 53 N/mm (p = 0.189) for the yield load and linear stiffness, respectively]. The 3× platelet concentration also did not significantly change the mean anteroposterior knee laxity at 30° and 90° of flexion [5× vs. 3×: 3.5 mm vs. 5.1 mm (p = 0.140), and 6.1 mm vs. 6.3 mm (p = 0.764)] but did result in a lower AP laxity at 60° [5× vs. 3×: 8.6 mm vs. 7.3 mm (p = 0.012)]. The decrease in platelet concentration from 5× to 3× to enhance suture repair of the ACL did not significantly harm the mechanical outcomes in this animal model. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1002–1007, 2011     

The epidural test dose in obstetric anesthesia: it is not obsolete

Many anesthesiologists have called for the abandonment of the epidural test dose in the obstetric patient, citing its lack of sensitivity and specificity. A test dose of lidocaine 1.5% with epinephrine 1:200,000, in combination with aspiration, is highly effective in detecting incorrect placement of an epidural catheter. If the catheter is intrathecal, it requires approximately 2 minutes to obtain a sensory level. For the detection of an intravascular catheter, a positive test dose would result in a sudden increase in the maternal heart rate of 10 beats per minute within 1 minute after injection. It should not be administered during uterine contraction, as labor pain may trigger a tachycardic response. This test dose has been extensively studied and is safe both for both mother and fetus.     

Verapamil is not a therapeutic adjunct to dantrolene in porcine malignant hyperthermia

We have investigated the hypothesis that the calcium antagonist verapamil might be useful for prevention or treatment of malignant hyperthermia (MH) in MH-susceptible (MHS) swine. MH episodes were triggered in four groups of four swine with halothane alone or combined with succinylcholine (SCh) and, with and without verapamil. MH episodes were reversed by therapy with dantrolene and NaHCO3 in all groups. Verapamil did not alter MH episodes triggered by halothane alone or combined with SCh. The dantrolene-NaHCO3 requirements for reversal of MH were greater for the groups receiving halothane-SCh, but did not differ in groups pretreated with and without verapamil. In vitro verapamil (25 microM) did not reduce responses of intact muscle fibers to halothane and, in fact, exaggerated some halothane-induced responses. High concentrations of verapamil (0.5 mM) caused contractures in MHS but not in normal muscles. Neither our in vivo nor in vitro results support the use of verapamil in the treatment of MH. Further, doses of dantrolene used to reverse these MH episodes, although admittedly small (1-2 mg/kg), did not produce myocardial depression when used in combination with verapamil.     

The epidural space is deeper in elderly and obese patients in the Japanese population

BACKGROUND: Epidural anaesthesia is an efficient method of providing both regional anaesthesia and post-operative pain relief. Detection of the epidural space is critical, but it is difficult to predict the depth of the epidural space. Published results are inconsistent. We retrospectively investigated the differences in the depth of the epidural space depending on the puncture site, approach type and physical findings of patients. METHODS: All surgical patients from 1994 to 2005 were included in the study and 4964 cases were analysed. The recorded distance from the needle tip to the skin surface was defined as the depth of the epidural. The differences in the depth were compared according to the puncture site, level and approach. We then searched for the factors determining the depth using multivariate regression analysis. RESULTS: The depth in upper thoracic sites (T1/2-T9/10) was 5.0 (1.0) cm [mean (SD), n= 465] via the midline approach and 5.2 (1.0) cm (n= 1226) via the paramedian approach. For lumbar sites, the depth was 4.1 (0.9) cm (n= 1835) via the midline approach and 4.6 (1.0) cm (n= 298) via the paramedian approach. In the multivariate regression analysis, patient age, body weight and more cephalad puncture were significantly and positively correlated with the depth at thoracic sites. CONCLUSIONS: The epidural space was deeper at upper thoracic sites than lower thoracic or lumbar sites. The depth with the paramedian approach was greater than with the midline approach at both sites. Patient age and weight were positive factors for depth.     

Experimental Bacteroides fragilis bacteremia in a primate model: evidence that Bacteroides fragilis does not promote the septic shock syndrome

Experimental Bacteroides fragilis bacteremia was studied in subhuman primates. Following intravenous infusion of viable B. fragilis there was an exponential clearance of organisms from the bloodstream. The major clearance organ was the liver, which accumulated 68.2% of the total inoculum. The most efficient clearance was exhibited by the spleen, with uptake of 1.16% gm tissue. Hemodynamic studies revealed no significant changes in heart rate, mean arterial pressure, or cardiac output following B. fragilis infusion. Complement activity as measured by CH50, alternative pathway hemolytic activity, granulocyte aggregometry, C4, C3, properdin, and Factor B levels were similarly unaffected by infusion of B. fragilis. In contrast, profound hemodynamic changes and a consistent decrease in complement activity was noted after challenge with S. minnesota. The results of this study suggest that B. fragilis bacteremia has a minor role in producing the acute hemodynamic changes associated with the septic shock syndrome.