Anneke C. Bush

Hydroxocobalamin and sodium thiosulfate versus sodium nitrite and sodium thiosulfate in the treatment of acute cyanide toxicity in a swine (Sus scrofa) model.

STUDY OBJECTIVE Cyanide can cause severe hypotension with acute toxicity. To our knowledge, no study has directly compared hydroxocobalamin and sodium nitrite with sodium thiosulfate in an acute cyanide toxicity model. Our objective is to compare the return to baseline of mean arterial blood pressure between 2 groups of swine with acute cyanide toxicity and treated with hydroxocobalamin with sodium thiosulfate or sodium nitrite with sodium thiosulfate. METHODS Twenty-four swine were intubated, anesthetized, and instrumented (continuous arterial and cardiac output monitoring) and then intoxicated with a continuous cyanide infusion until severe hypotension. The animals were divided into 2 arms of 12 each and then randomly assigned to intravenous hydroxocobalamin (150 mg/kg)+sodium thiosulfate (413 mg/kg) or sodium nitrite (10 mg/kg)+sodium thiosulfate (413 mg/kg) and monitored for 40 minutes after start of antidotal infusion. Twenty animals were needed for 80% power to detect a significant difference in outcomes (alpha 0.05). Repeated measures of analysis of covariance and post hoc t test were used for determining significance. RESULTS Baseline mean weights, time to hypotension (31 minutes 3 seconds versus 28 minutes 6 seconds), and cyanide dose at hypotension (5.6 versus 5.9 mg/kg) were similar. One animal in the hydroxocobalamin group and 2 animals in the sodium nitrite group died during antidote infusion and were excluded from analysis. Hydroxocobalamin resulted in a faster return to baseline mean arterial pressure, with improvement beginning at 5 minutes and lasting through the conclusion of the study (P<.05). No statistically significant difference was detected between groups for cardiac output, pulse rate, systemic vascular resistance, or mortality at 40 minutes post intoxication. Mean cyanide blood levels (4.03 versus 4.05 microg/mL) and lactate levels (peak 7.9 versus 8.1 mmol/L) at hypotension were similar. Lactate levels (5.1 versus 4.48 mmol/L), pH (7.40 versus 7.37), and base excess (-0.75 versus 1.27) at 40 minutes were also similar. CONCLUSION Hydroxocobalamin with sodium thiosulfate led to a faster return to baseline mean arterial pressure compared with sodium nitrite with sodium thiosulfate; however, there was no difference between the antidote combinations in mortality, serum acidosis, or serum lactate.

Hydroxocobalamin Versus Sodium Thiosulfate for the Treatment of Acute Cyanide Toxicity in a Swine (Sus scrofa) Model

STUDY OBJECTIVE We compare the efficacy of hydroxocobalamin to sodium thiosulfate to reverse the depressive effects on mean arterial pressure in a swine model of acute cyanide toxicity and gain a better understanding of the mechanism of action of the hydroxocobalamin in reversal of the toxicity. METHODS Swine were intubated, anesthetized, and instrumented with central arterial and venous lines and a pulmonary artery catheter. Animals (n=36) were randomly assigned to one of 3 groups: hydroxocobalamin alone (150 mg/kg), sodium thiosulfate alone (413 mg/kg), or hydroxocobalamin (150 mg/kg)+sodium thiosulfate (413 mg/kg) and monitored for 60 minutes after the start of antidotal infusion. Cyanide was infused until severe hypotension developed, defined as blood pressure 50% of baseline mean arterial pressure. Repeated-measures ANOVA was used to determine statistically significant changes between groups over time. RESULTS Time to hypotension (25, 28, and 33 minutes), cyanide dose at hypotension (4.7, 5.0, and 5.6 mg/kg), and mean cyanide blood levels (3.2, 3.7, and 3.8 μg/mL) and lactate levels (7, 8.2, 8.3 and mmol/L) were similar. All 12 animals in the sodium thiosulfate group died compared with 2 of 12 in the hydroxocobalamin/sodium thiosulfate group and 1 of 12 in hydroxocobalamin group. No statistically significant differences were detected between the hydroxocobalamin and hydroxocobalamin/sodium thiosulfate groups for carbon monoxide, mean arterial pressure, cyanide levels, or mortality at 60 minutes. Lactate level (2.6 versus 2.1 mmol/L), pH (7.44 versus 7.42), and bicarbonate level (25 versus 26 mEq/L) at 60 minutes were also similar between groups. CONCLUSION Sodium thiosulfate failed to reverse cyanide-induced shock in our swine model of severe cyanide toxicity. Further, sodium thiosulfate was not found to be effective when added to hydroxocobalamin in the treatment of cyanide-induced shock. Hydroxocobalamin alone was again found to be effective for severe cyanide toxicity.

C-reactive protein elevation independently influences the procedural success of percutaneous balloon mitral valve commissurotomy

Abstract Background Markers of systemic inflammation including C-reactive protein (CRP) appear to predict morbidity and mortality in various clinical conditions. The presence of systemic inflammation and its impact on the procedural success of percutaneous balloon mitral valve commissurotomy (PBMC) in patients with rheumatic mitral stenosis has not been previously demonstrated. Methods Measurements of CRP with a high-sensitivity assay were performed at the time of PBMC or during post-procedural follow-up in 119 patients with mitral stenosis of rheumatic morphology. Patients were questioned to exclude confounders of CRP elevation and categorized into undetectable (≤0.10 mg/L) and detectable (>0.10 mg/L) CRP levels. Detectable levels were further classified into assay range (>0.10 and ≤6.0 mg/L) and elevated (>6.0 mg/L). Results CRP was detectable in 76% of patients and elevated (>6.0 mg/L) in 36% of patients studied. Procedural success occurred in 89% of patients with undetectable CRP, as compared with only 67% in patients with detectable CRP (P = .028). This effect remained after controlling for age and valve score (previously described predictors of PBMC success). Conclusions Systemic inflammation is common in patients with rheumatic mitral valve stenosis, and the relationship between procedural success and CRP suggests persistent inflammation may affect the results of PBMC.

Predicting Irreparable Renal Ischemic Injury Using a Real-Time Marker in the Porcine Model

PURPOSE We determined the maximal renal tolerance of warm ischemia using renal cortical interstitial metabolic changes to identify a potential real-time marker of irreparable renal function. MATERIALS AND METHODS Using a single kidney model 3 groups of 5 pigs each underwent 120, 150 and 180 minutes of warm ischemia, respectively. Microdialysis samples were collected before, during and after ischemia. Renal function assessments consisting of serum creatinine and GFR measurements were performed before ischemia and on post-ischemia days 1, 5, 9, 14 and 28. Kidneys exposed and not exposed to ischemia were collected for histological study. RESULTS Interstitial glucose and pyruvate concentrations decreased, while lactate concentrations increased to stable levels during ischemia. Glutamate spiked at 30 minutes of ischemia and subsequently tapered, while glycerol increased throughout warm ischemia time. At post-ischemia day 28 renal function returned to pre-ischemia baseline levels in the group with 120 minutes of ischemia but did not recover to baseline in the 150 and 180-minute ischemic groups. Functional data correlated with histological findings. The 120-minute maximal renal tolerance of warm ischemia correlated with a mean +/- SD glycerol concentration of 167 +/- 24 micromol/l. CONCLUSIONS Interstitial glycerol is a real-time, renal unit specific, minimally invasive marker of renal function deterioration. Exposure of porcine kidneys to ischemic insults resulting in renal cortical interstitial glycerol concentrations higher than 167 micromol/l is associated with irreparable functional damage in this model.

Real-Time Analysis of Renal Interstitial Metabolites During Induced Renal Ischemia

PURPOSE Microdialysis is an innovative technique used to monitor the chemistry of the interstitial fluid in living tissue. We documented changes in concentration of interstitial fluid metabolites before, during, and after induced renal ischemia. MATERIALS AND METHODS Under general anesthesia, a microdialysis probe was laparoscopically positioned into the renal cortex of six pigs. Isotonic sterile perfusion fluid was pumped through the probe at 2 microL/min. After collecting a baseline sample, the renal artery was occluded with a Satinsky clamp for 90 (n = 3) or 120 (n = 3) minutes. A dialysate sample was collected every 30 minutes during the ischemic and 3-hour postischemic period. The samples were analyzed for glucose, lactate, pyruvate, glutamate, urea, and glycerol concentrations with the CMA/600 Microdialysis Analyzer. Serum metabolic panels from peripheral venous samples drawn before ischemia, after ischemia, and 3 hours after ischemia were analyzed. RESULTS Glucose and pyruvate concentrations significantly declined (P = 0.01, P = 0.05, respectively) while lactate and glycerol concentrations significantly increased during ischemia (P = <0.01, P < 0.01, respectively). Glutamate increased to 2.5 times the baseline concentration (P < 0.01) at 1 hour of ischemia and subsequently declined during ischemia. The lactate/pyruvate ratio increased sharply during ischemia and returned to baseline within 1 hour postischemia. There were no changes noted in serum creatinine levels before and after ischemia. CONCLUSIONS Microdialysis can accurately measure minute real-time changes in the renal interstitial environment caused by ischemia not detected with serum studies. These local changes may be correlated with ischemic times to predict tissue preservation in future studies.

Hydroxocobalamin and Epinephrine Both Improve Survival in a Swine Model of Cyanide-Induced Cardiac Arrest

STUDY OBJECTIVE To determine whether hydroxocobalamin will improve survival compared with epinephrine and saline solution controls in a model of cyanide-induced cardiac arrest. METHODS Forty-five swine (38 to 42 kg) were tracheally intubated, anesthetized, and central venous and arterial continuous cardiovascular monitoring catheters were inserted. Potassium cyanide was infused until cardiac arrest developed, defined as mean arterial pressure less than 30 mm Hg. Animals were treated with standardized mechanical chest compressions and were randomly assigned to receive one of 3 intravenous bolus therapies: hydroxocobalamin, epinephrine, or saline solution (control). All animals were monitored for 60 minutes after cardiac arrest. Additional epinephrine infusions were used in all arms of the study after return of spontaneous circulation for systolic blood pressure less than 90 mm Hg. A sample size of 15 animals per group was determined according to a power of 80%, a survival difference of 0.5, and an α of 0.05. Repeated-measure ANOVA was used to determine statistically significant changes between groups over time. RESULTS Baseline weight, time to arrest, and cyanide dose at cardiac arrest were similar in the 3 groups. Coronary perfusion pressures with chest compressions were greater than 15 mm Hg in both treatment groups indicating sufficient compression depth. Zero of 15 (95% confidence interval [CI] 0% to 25%) animals in the control group, 11 of 15 (73%; 95% CI 48% to 90%) in the hydroxocobalamin group, and 11 of 15 (73%; 95% CI 48% to 90%) in the epinephrine group survived to the conclusion of the study (P<.001). The proportion of animals with return of spontaneous circulation at 5 minutes was 4 of 15 (27%; 95% CI 10% to 52%), and that of return of spontaneous circulation at 10 minutes was 11 of 15 (73%; 95% CI 48% to 90%) in the 2 treatment groups. Additional epinephrine infusion after return of spontaneous circulation was administered for hypotension in 2 of 11 (18%; 95% CI 4% to 48%) hydroxocobalamin animals and in 11 of 11 (100%; 95% CI 70% to 100%) of the epinephrine animals (P<.001). At 60 minutes, serum lactate was significantly lower in the hydroxocobalamin group compared with the epinephrine group (4.9 [SD 2.2] versus 12.3 [SD 2.2] mmol/L), and the pH was significantly higher (7.34 [SD 0.03] versus 7.15 [SD 0.07]). Serial blood cyanide levels in the hydroxocobalamin group were also lower than that of the epinephrine group from cardiac arrest through the conclusion of the study. CONCLUSION Intravenous hydroxocobalamin and epinephrine both independently improved survival compared with saline solution control in our swine model of cyanide-induced cardiac arrest. Hydroxocobalamin improved mean arterial pressure and pH, decreased blood lactate and cyanide levels, and decreased the use of rescue epinephrine therapy compared with that in the epinephrine group.

A Comparison of Proximal Tibia, Distal Femur, and Proximal Humerus Infusion Rates Using the EZ-IO Intraosseous Device on the Adult Swine (Sus scrofa) Model

Abstract Objective. We sought to compare the flow rates of the proximal tibia, the distal femur, and the proximal humerus using high pressure (greater than 300 mmHg) through an intraosseous (IO) infusion needle in an adult swine model. Methods. We performed a prospective interventional study in 11 swine. After placement of central vein and arterial lines, blood was removed via the central line until the animals mean arterial pressure decreased 25% from the recorded baseline. We inserted a 25-mm IO needle into the proximal tibia and 45-mm needles into the distal femur and proximal humerus. All extremities were utilized in each study animal. We infused normal saline at each site for 10 minutes with a pressure bag inflated to the highest achievable pressure (greater than 300 mmHg) as measured at the infusion site with a calibrated portable inline pressure gauge. We measured the volume of normal saline remaining and we calculated infusion rates for each site. We then compared infusion flow rates between the three locations. Statistical analysis and comparison of the infusion rates of all three study arms were as performed using analysis of variance (ANOVA). Results. The average weight of the swine was 71 kg (range 64–84 kg). Successful placement of the IO needle was confirmed at all three sites. The mean infusion flow rate was 213 mL/min (standard deviation [SD] 53.2 mL/min) for the proximal humerus, 138 mL/min (SD 65.3 mL/min) for the distal femur, and 103 mL/min (SD 48.1 mL/min) for the proximal tibia (p < 0.001). The flow rate through the proximal humerus was statistically greater than that for the proximal tibia and the distal femur (p < 0.001). The flow rates through the proximal tibia and distal femur were similar. Conclusion. The humerus is a suitable alternative site for IO placement, with a potential for higher flow rates than the proximal tibia and distal femur when resuscitating a patient. Key words: intraosseous; prehospital; resuscitation; tactical combat casualty care; emergency medical services

Reflex High-Risk Human Papillomavirus Testing for Women With Atypical Squamous Cells of Undetermined Significance in Cytologic Smears Effects Since Implementation in a Large Clinical Practice

Reflex high-risk human papillomavirus (HPV) testing often is used in the management of women with atypical squamous cells of undetermined significance identified in cervicovaginal screening. Following implementation of reflex testing, our laboratory processed 8,022 specimens during a 20-month period; sufficient material was available for testing in 7,334 specimens. High-risk HPV was detected in 34.10% of these specimens. Detection rates varied with age, with positive rates as high as 58.46% in women 20 years old or younger, decreasing to 14.58% in women older than 35 years. The detection rate, categorized in 5-year age increments, showed a significant decrease until after 35 years, when the rate remained fairly constant (P < .0001). The detection rate decreased over the time of the study. These results demonstrate that high-risk HPV detection might vary according to the age mix of the population tested and the interval after implementation of testing.

Reflex High-Risk Human Papillomavirus Testing for Women With Atypical Squamous Cells of Undetermined Significance in Cytologic Smears

Reflex high-risk human papillomavirus (HPV) testing often is used in the management of women with atypical squamous cells of undetermined significance identified in cervicovaginal screening. Following implementation of reflex testing, our laboratory processed 8,022 specimens during a 20-month period; sufficient material was available for testing in 7,334 specimens. High-risk HPV was detected in 34.10% of these specimens. Detection rates varied with age, with positive rates as high as 58.46% in women 20 years old or younger, decreasing to 14.58% in women older than 35 years. The detection rate, categorized in 5-year age increments, showed a significant decrease until after 35 years, when the rate remained fairly constant ( P < .0001). The detection rate decreased over the time of the study. These results demonstrate that high-risk HPV detection might vary according to the age mix of the population tested and the interval after implementation of testing.

Lapra-Ty Holding Strength and Slippage with Various Suture Types and Sizes

OBJECTIVES To investigate the holding strength and slippage of Lapra-Ty clips on various suture types and sizes. METHODS Using an automated materials testing system with the Lapra-Ty in a fixed position, Lapra-Ty holding strength and displacement were determined with 0, 2-0, 3-0, and 4-0 Vicryl, Monocryl, and polydioxanone suture (PDS). To simulate clinical application, Lapra-Tys were also tested by applying a load to these sutures after being passed through a full-thickness layer of tautly suspended fresh porcine bladder tissue. Three trials were performed with each suture type and size. RESULTS The Lapra-Ty holding strength with Vicryl suture was significantly higher than with Monocryl or PDS of the same suture size in bladder tissue trials. Monocryl suture had a significantly higher displacement than Vicryl or PDS of the same suture size in bladder tissue trials (except for 4-0 Monocryl and PDS having insignificantly different displacements). Lapra-Tys slipped off Vicryl, Monocryl, and PDS in 25%, 67%, and 67% of their respective trials. Lapra-Tys did not slip during any of the trials with 2-0 suture of any type or 3-0 Vicryl. Lapra-Tys with holding strengths on suture less than approximately 8 Newtons (N) slipped and greater than 8 N pulled through the bladder tissue without slipping. CONCLUSIONS The optimal suture type and size to maximize Lapra-Ty holding strength and minimize slippage was determined to be 2-0 and 3-0 Vicryl, 2-0 Monocryl, and 2-0 PDS. Monocryl suture stretches more than Vicryl and PDS at higher loads.