The safety of protamine sulfate in diabetics undergoing cardiac catheterization

The frequency of anaphylactoid reactions to protamine sulfate was examined by reviewing the records of diabetic patients undergoing cardiac catheterization over a 5-year period, and by prospectively monitoring diabetic patients receiving NPH insulin during the infusion of protamine sulfate. No anaphylactoid reactions were noted after protamine administration (48 +/- 5 mg) in the retrospective study in either patients with prior exposure to protamine (74 catheterizations) or in diabetics with no exposure to protamine (132 catheterizations). In the prospective study, no anaphylactoid reactions were seen in the 24 NPH insulin-dependent diabetics during the infusion of protamine sulfate (45 +/- 5 mg). Five of the 42 patients (12%) from the retrospective study who underwent vascular surgery developed severe reactions to much larger doses of protamine (380 +/- 118 mg). Diabetics with prior exposure to protamine sulfate do not appear to be at increased risk of anaphylactoid reaction after the administration of protamine sulfate in the dose range of less than 50 mg at the time of cardiac catheterization.     

The contemporary role of protamine in the cardiac catheterization laboratory

Access to the arterial circulation and full anticoagulation carries a risk of serious bleeding during and after percutaneous coronary intervention. Important sources of bleeding include the arterial access site and coronary artery perforation. Prompt and effective management of hemorrhagic complications is an essential interventional skill. Protamine sulfate is well-known as a heparin reversal agent. Despite this, there is heterogeneity in the use of protamine during interventional procedures. While protamine is generally well-tolerated, it is associated with a risk of hypersensitivity reaction, including anaphylaxis, among others. The purpose of this review is to summarize the existing evidence about and experience with the use of protamine sulfate in the setting of percutaneous coronary and structural interventional procedures.     

Pyrogenic reactions in patients undergoing cardiac catheterization associated with contaminated glass medicine cups

Pyrogenic reactions are potentially life-threatening complications caused by bacterial endotoxin. After two cardiac catheterization patients developed rigors the same day, the procedures were halted and a case control study was conducted. To identify case patients (persons with rigors ≤3 hr after catheterization during September 25–November 9, 1995), we reviewed medical records of all cardiac catheterization patients who had a blood culture or received intravenous meperidine. Twelve case patients and 40 randomly selected control patients were identified. No specific catheter was associated with case patients, but exposure to intracoronary-nitroglycerin (NTG) was (odds ratio = 12.0; 95% confidence interval 2.2, 75.6). NTG or indocyanine green dye was poured into glass medicine cups previously washed in an enzyme cleaner and then sterilized. The cleaner, used for an entire day, had elevated levels of gram-negative bacteria (≥10⁴ colony forming units/mL) and endotoxin (434 endotoxin units [EU]/mL]); the reprocessed cups had no live bacteria but had elevated endotoxin levels (median 2,250 EU). Exposure to contaminated glass medicine cups probably resulted in pyrogenic reactions and contributed to death in two critically ill patients. Cathet. Cardiovasc. Diagn. 42:12–18, 1997. Published 1997 Wiley-Liss, Inc.     

Successful cardiopulmonary bypass in diabetics with anaphylactoid reactions to protamine.

Two insulin dependent diabetics with previous anaphylactic like (anaphylactoid) reactions to protamine underwent successful cardiopulmonary bypass for coronary artery surgery. Platelet concentrates instead of protamine were used to neutralise their systemic heparinisation. In both cases the anaphylactoid reactions first became apparent after administration of protamine sulphate at the end of cardiac catheterisation. These cases show that adverse reactions to protamine need not be a contraindication to cardiopulmonary bypass and cardiac surgery and emphasise that this condition should be considered in all patients with a history of previous protamine exposure or one which may be associated with anaphylactoid reactions to protamine.     

Contrast-induced nephrotoxicity in patients undergoing cardiac catheterization

Contrast-induced nephrotoxicity (CIN) is a common concern among angiographers. The causes of CIN are not well understood and the identification and preparation of patients at risk are important. This report reviews the literature concerning the causes and identification of patients at risk and documents the studies that are available to improve the safety of cardiac catheterization and cardiac interventions by reducing the risk of CIN.     

Ketamine-etomidate for children undergoing cardiac catheterization

The purpose of this study was to determine the effects of combined low-dose ketamine and etomidate on hemodynamics during cardiac catheterization in children with congenital cardiac shunts. Sixty children undergoing routine diagnostic cardiac catheterization were included: 30 had a right-to-left shunt, and 30 had a left-to-right shunt. Both groups were given a single dose of etomidate 0.3 mg·kg(-1) with ketamine 1 mg·kg(-1). There were no hemodynamic changes in the group with a right-to-left shunt. In cases of left-to-right shunt, there were significant differences in heart rate, right atrial pressure, mean arterial pressure, mean pulmonary artery pressure, pulmonary artery wedge pressure, and systemic vascular resistance index. Decreases in pulmonary blood flow and pulmonary-systemic shunt ratio were also observed. Further studies are required with dose titration of this anesthetic combination in pediatric patients with congenital heart disease involving a left-to-right shunt.     

Adverse reactions to protamine sulfate following cardiac surgery

We report four patients who developed severe adverse reactions to protamine sulfate following cardiac surgery. Two types of reactions were seen. First, an immediate anaphylaxis which is a complement-dependent IgG antibody-mediated reaction. In the literature, 80% of patients who had similar reactions have had previous exposure to protamine. All patients adequately tested had positive skin tests and there is 6% mortality. The second reaction to protamine during cardiac surgery is characterized by delayed onset and profound vascular damage presenting as noncardiogenic pulmonary edema or total vascular collapse with prolonged hypotension and anasarca. These patients have negative skin tests and in our studies, no evidence of antibody mediated reaction, suggesting some other mechanisms may play a part. The mortality is high (30% of patients reported) and survivors have significant morbidity.     

Anticoagulation with heparin during cardiac catheterization and its reversal by protamine

The duration of effective anticoagulation with heparin during cardiac catheterization and angiography was determined in 201 patients. Effective anticoagulation was defined as prolongation of the activated partial thromboplastin time (APTT) by 2 or more times the upper limit of normal. When the procedure was completed within 40 min of heparin administration, all patients were anticoagulated adequately. The incidence of inadequate anticoagulation ranged from 9% to 25% as the time from heparin administration increased to 89 min. Procedures completed more than 90 min after heparin administration had a 58% incidence of inadequate anticoagulation. A protocol to estimate the appropriate protamine dose was developed based on experience accumulated in the first 78 patients and tested subsequently in 101 consecutive patients. Clotting studies returned to the normal range in 92% of the patients. The mean APTT decreased from 84.1 +/- 19.4 to 27.4 +/- 2.5 sec (p less than .001) after protamine. Patients who did not correct to normal after protamine remained only 2.8 +/- 1.4 sec (range 0.7-5.5 sec) above normal. These data provide an estimate of the duration of anticoagulation during cardiac catheterization and angiography and demonstrate the feasibility of a simple and reliable method to reverse the effects of heparin.     

Protamine allergy reactions during cardiac catheterization and cardiac surgery: risk in patients taking protamine-insulin preparations.

Protamine insulin use may immunologically sensitize patients to protamine, leading to anaphylactoid reactions upon subsequent exposure to protamine sulfate during cardiac catheterization or cardiovascular surgery. The risk of such reactions in protamine insulin-dependent patients is uncertain. One catheterization study reported a 50-fold greater risk while a second showed no increased risk! To clarify the risk, the records of 7,750 cardiac catheterization procedures between 1984 and 1987 were analyzed for presence of NPH or PZI insulin use, protamine administration, and any complications or adverse reactions. Protamine was administered in 3,341/7,750 procedures (43%), including 171 in diabetics receiving NPH insulin. Adverse reactions to protamine occurred in 2/3, 170 noninsulin patients, 0.06%, and adverse reactions due to probable NPH insulin sensitization occurred in 1/171, 0.6%, of NPH diabetics, p = .034. Meta-analysis of risk showed an odds ratio of 7.96 for the NPH diabetic patients, and combining these results with the other large series in the literature (269 NPH diabetics total) showed an odds ratio of 4.19 compared to a non-NPH insulin group. Meta-analysis of the surgical literature showed the risk in surgical patients to be 2.1% in NPH patients versus 0.12% with no NPH, with an odds ratio of 15.52. The greater incidence in surgical patients may be due to protamine sensitization at prior catheterization and to the larger dose of protamine administered to surgical patients.     

Increased arachidonic acid uptake by platelets from insulin-dependent diabetics and diabetic rats

14C-Arachidonic acid uptake was measured in platelets obtained from 15 insulin-dependent diabetic and 17 control subjects and in 12 streptozotocin-diabetic and 21 control rats. The 14C-arachidonic acid uptake, expressed as pmol/10(8) platelets/min, mean +/- SEM, was significantly higher in platelets from diabetic subjects (2.80 +/- 0.23) and diabetic rats (1.73 +/- 0.20) than in the control subjects (2.29 +/- 0.15) and the control rats (1.35 +/- 0.08). No significant correlations were found between arachidonic acid uptake and glucose, total cholesterol or triglyceride plasma levels in either rats or humans. Arachidonic acid uptake was inhibited by indometacin but not by nordihydroguaiaretic acid, in diabetic as well as in control subjects. The present results suggest that the increased arachidonic acid uptake by platelets from insulin-dependent diabetic patients and streptozotocin-diabetic rats depends on their increased platelet arachidonic acid utilization through the cyclooxygenase pathway.     

Value of right-sided cardiac catheterization in patients undergoing left-sided cardiac catheterization for evaluation of coronary artery disease

The value of right-sided cardiac catheterization was assessed prospectively in 200 patients undergoing left-sided catheterization for evaluation of known or suspected coronary artery disease. Before catheterization, data from right-sided catheterization was not felt to be necessary for clinical management. There were 6 +/- 2 extra minutes of procedure time and 86 +/- 63 extra seconds of fluoroscopy time used. Abnormalities were detected in 69 (35%) patients. These findings were unexpected in 37 of these patients and in 3 patients, further evaluation was prompted. However, management was altered in only 3 (1.5%) patients as a result of data obtained by right-sided catheterization. In conclusion this additional procedure rarely adds clinically useful information about patients undergoing left-sided catheterization and angiography for coronary artery disease without a clinical indication for right-sided catheterization.     

Accurate measurement of oxygen consumption in children undergoing cardiac catheterization

Oxygen consumption (VO₂) is an important part of hemodynamics using the direct Fick principle in children undergoing cardiac catheterization. Accurate measurement of VO₂ is vital. Obviously, any error in the measurement of VO₂ will translate directly into an equivalent percentage under‐ or overestimation of blood flows and vascular resistances. It remains common practice to estimate VO₂ values from published predictive equations. Among these, the LaFarge equation is the most commonly used equation and gives the closest estimation with the least bias and limits of agreement. However, considerable errors are introduced by the LaFarge equation, particularly in children younger than 3 years of age. Respiratory mass spectrometry remains the “state‐of‐the‐art” method, allowing highly sensitive, rapid and simultaneous measurement of multiple gas fractions. The AMIS 2000 quadrupole respiratory mass spectrometer system has been adapted to measure VO₂ in children under mechanical ventilation with pediatric ventilators during cardiac catheterization. The small sampling rate, fast response time and long tubes make the equipment a unique and powerful tool for bedside continuous measurement of VO₂ in cardiac catheterization for both clinical and research purposes. © 2012 Wiley Periodicals, Inc.     

Patency of the interatrial septum in children undergoing cardiac catheterization

Catheter passage into the left atrium from the right atrium greatly facilitates invasive cardiovascular evaluation and reduces the risks attendant on cardiac catheterization studies. We reviewed 371 consecutive cardiac catheterizations to establish the presence of natural interatrial communications. Catheter course, pressure equalization, and left-to-right atrial shunt on recirculation angiography were considered to determine intact interatrial septum (IIS), patent foramen ovale (PFO) or atrial septal defect (ASD). During the first year of life, 88% of infants had PFO or ASD; in 12%, the interatrial septum was intact. In children 1–10 years old, 49% had IIS, 27% had PFO, and 24% had ASD. In children 10–21 years old, 24% had PFO, or ASD. Though there seems to be a greater likelihood of ISS in those with left heart obstruction, hemodynamic factors did not completely explain the timing of closure of the foramen ovale. Presence of an interatrial communication allows catheter entrance into all left heart structures including the aorta; therefore, in patients with PFO or ASD, retrograde arterial procedure or transseptal puncture technique can be avoided when performing left heart catheterization. This appears possible in 88% of those under 1 year of age, in 51% of those 1–10 years old, and in 24% of children 10–21 years old.     

Prevalence of renal artery stenosis in patients undergoing cardiac catheterization

To investigate the prevalence of significant renal artery stenosis (RAS ≥50%), and to identify clinical predictors for significant RAS in patients with an elevated cardiovascular risk, such as those affected by ischemic heart disease. In patients with an elevated cardio-vascular risk, both atherosclerotic renovascular disease and coronary artery disease (CAD) are likely to occur. Prospectively from April 2007 to March 2008, all consecutive patients with ischemic heart disease undergoing non-emergent cardiac catheterization were also evaluated for atherosclerotic RAS by renal arteriography. A RAS ≥50% was considered as significant. A total of 1,298 patients underwent cardiac and renal angiography. Significant RAS was found in 70 out of 1,298 patients (5.4%). The presence of peripheral vascular disease, eGFR <67 ml/min/1.73 m², age >66 years, dyslipidemia, CAD severity and pulse pressure >52 mmHg were independent clinical predictors of significant RAS, and jointly produced a ROC AUC of 0.79 (95% CI 0.73–0.85, P < 0.001). Based on these data, a prediction rule for significant RAS was developed, and it showed an adequate predictive performance with 64% sensitivity and 82% specificity. In a large cohort of patients undergoing coronary angiography, significant RAS is a relatively rare comorbidity (5.4%). A model based on simple clinical variables may be useful for the clinical identification of high CV risk patients who may be suitable for renal arteriography at the time of cardiac catheterization.     

Visual evoked potentials in insulin-dependent diabetics

Summary The latency of pattern-reversal VEPs was studied in type I insulin-dependent diabetics without retinal and extraocular involvement. One hundred eyes of 50 diabetics (mean age 19.8±7.2 years) formed the study group; the duration of the disease ranged between 1 month and 15 years. The latencies of VEPs were progressively delayed in relation to the duration of the disease, becoming more and more evident and stabilizing after about 6 years from the onset of diabetes. The VEP alterations probably indicate alteration of membrane balance or demyelinization.     

QT dispersion in insulin-dependent diabetics]

BACKGROUND: The measurement of the dispersion of the QT interval reflects regional repolarization differences in the heart which in turn can elicit the onset of arrhythmias by means of re-entry mechanism. Therefore, inter-lead QT dispersion has been proposed as novel indicator of arrhythmogenic risk that can predict severe ventricular arrhythmias or sudden death. The present study was conducted to evaluate QT dispersion in diabetic insulin-dependent patients with autonomic neuropathy. METHODS: We recruited three groups of 10 patients with the same age, sex, body weight distribution: 1) group DAN+ (diabetics with neuropathy); 2) group DAN- (diabetics without neuropathy); and 3) group CTRL (healthy control group). The patients underwent two-dimensional color-Doppler echocardiography and 12-lead electrocardiogram, 25 and 50 mm/s paper speed (gain 10 mm/mU). The QTc dispersion was determined as the difference between the maximum and the minimum value of the QTc interval in different leads of the ECG recording. QT interval was corrected (QTc) by heart rate according to the Bazett's formula. Cardiovascular autonomic function was evaluated by Ewing's tests (heart rate and blood pressure measurement during lying to standing, deep breathing, hand-grip isometric stress test and Valsalva's maneuver). RESULTS: QT dispersion was significantly greater (p < 0.01) in the patients with autonomic neuropathy (51 +/- 10 ms) than in the patients without autonomic neuropathy (29 +/- 6 ms) or in healthy control subjects (26 +/- 5 ms). CONCLUSIONS: Our data suggest that diabetic neuropathy, associated with an increased QT dispersion, shows a higher risk for serious ventricular arrhythmias and sudden cardiac death.     

Increased kidney size,glomerular filtration rate and renal plasma flow in short-term insulin-dependent diabetics

Summary Glomerular filtration rate (GFR), renal plasma flow (RPF) and kidney volume were measured in thirteen male subjects (mean age 30 years) with short-term insulin-dependent diabetes (mean duration of disease 2.4 years) and fourteen normal male subjects (mean age 29 years). GFR and RPF were measured by constant infusion technique using I¹²⁵-iothalamate and ¹³¹I-hippuran. Kidney size was determined by means of ultrasound. GFR, RPF and kidney volume were increased in the diabetic patients compared to the normal controls, 144 versus 113 ml/ min×1.73m² (p<0.0005), 627 versus 523 ml/ min×1.73 m² (p<0.0025) and 278 versus 224 ml/ 1.73 m² (p<0.0005) respectively. Combining results from diabetic patients and controls revealed a positive correlation between kidney size and GFR (r= 0.70, p<0.001) and between kidney size and RPF (r=0.61, p<0.001). Within the groups kidney size and RPF correlated significantly in the diabetics (p< 0.01) and the same was found for kidney size and GFR (0.025< p<0.05), while no correlations were found in the normal group. GFR and RPF correlated in the diabetics when evaluated separately (r=0.81, p<0.001) and in the controls (r=0.73, p<0.001). The previous and present data suggest that the mechanisms of the elevated GFR in insulin-dependent diabetics are enhanced RPF, increased transglomerular hydrostatic pressure gradient and increased glomerular ultrafiltration coefficient. The increased kidney size is probably the main cause of the above alterations in the GFR determinants.