Nabil R. Fahmy

Blood-gas and circulatory changes during total knee replacement. Role of the intramedullary alignment rod.

The use of an intramedullary alignment rod in the distal part of the femur is an important step in performing total knee-replacement arthroplasty. On the basis of our observation of a sudden decrease in oxygen saturation in some patients after insertion of the rod, a prospective study was done of the circulatory and blood-gas changes that were associated with insertion in thirty-five patients. We examined the effects of the use of an eight-millimeter solid alignment rod, with and without venting; an eight-millimeter fluted alignment rod, with venting; and an eight-millimeter fluted or solid alignment rod, inserted through a 12.7-millimeter drill-hole, but without other venting. A statistically significant reduction in oxygen saturation, arterial oxygen tension (PaO2), and end-tidal carbon-dioxide tension (PETCO2) occurred after insertion of both solid and fluted eight-millimeter alignment rods through an eight-millimeter hold in both vented and unvented femoral canals, in association with a significant increase (p less than 0.01) in intramedullary pressure. Bone-marrow contents and fat were retrieved from samples of blood from the right atrium, indicating that embolization of marrow contents had occurred during insertion of the alignment rod. A small decrease in systemic blood pressure and heart rate also occurred. These changes were completely eliminated by the use of a 12.7-millimeter drill-hole as the entry site of the eight-millimeter fluted rod. We concluded that insertion of an intramedullary alignment rod in the femur causes embolization of marrow contents, which decreases arterial oxygen tension, oxygen saturation, end-tidal carbon-dioxide tension, arterial blood pressure, and heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of histamine in the hemodynamic and plasma catecholamine responses to morphine

The role of histamine in the hemodynamic and plasma catecholamine responses to intravenous morphine in subjects without cardiovascular disease and not receiving prior medication has not been reported. Systemic hemodynamics and serum histamine and plasma catecholamine concentrations were measured in 10 subjects before and 2, 5, 10, and 20 min after, 0.3 mg kg−1 IV morphine. Serum histamine concentration increased 2, 5, and 10 min after the morphine. Systolic and mean arterial pressures and systemic vascular resistance decreased and cardiac output increased because of increases in heart rate and stroke volume. The most important changes in hemodynamic function occurred after 2 min in association with a 400% increase in serum histamine concentration; these variables, together with serum histamine concentration, returned toward baseline values after 20 min. There was a negative correlation between peak increase in serum histamine concentration and maximum decrease in systemic vascular resistance. Plasma epinephrine concentrations were elevated 5, 10, and 20 min after morphine injection, suggesting activation of the adrenal medulla by histamine. Our data suggest that histamine plays an important role in the acute hemodynamic and plasma epinephrine response to morphine.

Diazepam prevents some adverse effects of succinyicholine

Neuromuscular, circulatory, and adverse effects of intravenous succinyicholine (SCh), 1 mg/kg, were compared in 3 groups of 40 patients each. Group I served as control; group II received diazepam, 0.05 mg/kg, 5 min before SCh; and group III was given d‐tubocurarine (d‐Tc), 0.05 mg/kg, for pretreatment. Diazepam pretreatment prevented muscle fasciculations, increases in serum potassium (K+) and creatinine phosphokinase (CPK) levels, increased heart rate and arterial pressure, and postoperative myalgia associated with SCh administration. The neuromuscular blocking action of SCh was not affected. Pretreatment with d‐Tc did not abolish increases in serum K+ and CPK levels, was associated with a higher incidence of postoperative myalgia, and decreased the onset and magnitude of SCh‐induced muscle paralysis. Our data demonstrate that diazepam, a predominant centrally acting muscle relaxant, is more effective than d‐Tc in preventing the adverse effects of SCh, a peripherally acting muscle relaxant.

Effects of trimethaphan on arterial blood histamine and systemic hemodynamics in humans.

Because of lack of direct evidence of histamine release by trimethaphan, the authors determined serum histamine levels and hemodynamic responses to trimethaphan administration in 19 consecutive patients. Group 1 patients (n = 7) received a single intravenous injection of trimethaphan, 0.5 mg · kg−1, while awake and again during stable halothane-nitrous oxide anesthesia. Group 2 patients (n = 6) were pretreated with intravenous H1 (chlorpheniramine, 0.1 mg · kg−1) and H2 (cimetidine, 4 mg · kg−1) receptor antagonists administered 15 min before trimethaphan, 0.5 mg · kg−1, in the awake and anesthetized states. In Group 3 (n = 6), the effects of infusion of trimethaphan, 3 mg · min−1 for 15 min, were studied during halothane-nitrous oxide anesthesia. In Group 1, bolus doses of trimethaphan were associated with maximal increases in serum histamine from 0.56 ± 0.14 to 2.56 ± 0.35 ng · ml−1 (P < 0.01) and from 0.60 ± 0.11 to 2.58 ± 0.33 ng · ml−1 (P < 0.01) 2 min after drug administration in the awake and anesthetized states, respectively; there were also clinical manifestations of histamine release. Mean arterial pressure decreased maximally after 5 min in the awake (from 92.0 ± 3.4 to 69.9 ± 2.2 mmHg; P < 0.01) and anesthetized (from 82.6 ± 3.7 to 57.3 ± 2.5 mmHg; P < 0.01) states, and was associated with increases in cardiac output and heart rate; stroke volume increased in the awake state only. Pretreatment with H1 and H2 receptor antagonists did not modify the hemodynamic response to trimethaphan, despite increases in serum histamine levels comparable to Group 1. In contrast to Group 1, although trimethaphan infusion caused a significant (P < 0.05) increase in serum histamine concentration from 0.72 ± 0.1 to 1.1 ± 0.1 ng · ml−1, the hypotension achieved was not associated with significant alterations in heart rate or cardiac output. In all patients, trimethaphan-induced hypotension was associated with a significant decrease in systemic vascular resistance, an effect that probably was related to the ganglionic blocking, direct vasodilating and alpha-adrenergic blocking action of trimethaphan. The authors conclude that histamine release by trimethaphan does not play an important role in the hemodynamic effects of the drug in humans.

Nitroprusside vs. a nitroprusside-trimethaphan mixture for induced hypotension: hemodynamic effects and cyanide release.

Changes in hemodynamic variables and whole blood cyanide and plasma thiocyanate concentrations associated with the infusion of sodium nitroprusside were compared with those during administration of a mixture of sodium nitroprusside (25 mg) and trimethaphan camsylate (250 mg) in a solution of 5% dextrose in water in twenty subjects who required deliberate hypotension for major orthopedic procedures. Subjects were randomly assigned to receive nitroprusside alone (group 1; n = 10) or the nitroprusside‐trimethaphan mixture (group 2; n = 10). All subjects received a similar anesthetic technique, consisting of 5 mg/kg thiopental, 1 mg/kg succinylcholine, 1% halothane, 0.2 mg/kg metocurine, and 60% nitrous oxide in oxygen. Mean arterial pressure decreased and was maintained at 55 mm Hg for 258 ± 4 and 266 ± 8 minutes in groups 1 and 2. Arterial hypotension was associated with a rise in cardiac output and heart rate in group 1 but not in group 2. Subjects in group 2 required less nitroprusside than did those in group 1 (1.39 ± 0.3 and 5.82 ± 0.63 µg/kg/min) because of the synergistic or additive action of the combination. After 4 hours of hypotension, the whole blood cyanide level rose from 3.5 ± 1.1 to 96.6 ± 14.0 µg/dl (1.35 ± 0.27 to 37.2 ± 5.4 µmol/L) in group 1 and from 3.7 ± 1.1 to 22.7 ± 4.2 µg/dl (1.42 ± 0.4 to 8.7 ± 1.6 µmol/L) in group 2. Plasma thiocyanate levels rose 2 hours after nitroprusside termination. Significant changes in pH and base deficit occurred late in the course of hypotension in group 1 only; there was a correlation (r = 0.896) between peak blood cyanide levels and decreases in base excess. A rebound increase in mean arterial pressure after termination of hypotension occurred only in group 1. Mean blood pressure increased an average of 13.5 (range 6 to 27) and 21.5 (range 8 to 32) mm Hg over the prehypotension and awake levels. Blood pressure was maximally increased 15 minutes after the end of the infusion and was associated with an increase in systemic vascular resistance; cardiac output did not change. One subject developed ST segment depression and required reinstitution of nitroprusside infusion. There were no adverse effects during or after cessation of the drug mixture.

Propranolol prevents hemodynamic and humoral events after abrupt withdrawal of nitroprusside

Hemodynamic and humoral events after intraoperative discontinuation of nitroprusside were studied in subjects without and with pretreatment with intravenous propranolol, 0.1 mg · kg−1 Nitroprusside‐induced hypotension was associated with increases in heart rate, cardiac output, plasma renin activity (PRA), and catecholamine levels; these changes were prevented by propranolol. In subjects pretreated with propranolol, dose requirements of nitroprusside for hypotension of comparable degree and duration decreased 40%. On discontinuation of nitroprusside, mean systemic pressure rose to 100.2 mm Hg—a level higher than prehypotension and awake values—because of increased systemic vascular resistance. Hemodynamic events were associated with persistent elevations of PRA and catecholamine levels. These rebound changes were maximal 15 min after nitroprusside withdrawal and returned to control levels 30 to 60 min later. Pretreatment with propranolol completely prevented rebound hemodynamic events after nitroprusside. Persistent elevations of PRA and catecholamine levels after nitroprusside action subsided were responsible for the effects of withdrawal.

Consumption of Vitamin B12 during Sodium Nitroprusside Administration in Humans

In view of evidence suggesting possible participation of cobalamin in cyanide metabolism, the effects of sodium nitro-prusside (SNP) infusion on blood cyanide and plasma thiocyanate levels and serum vitamin B12 levels were examined in ten patients undergoing major orthopedic procedures. Whole blood cyanide concentrations increased significantly (P < 0.001) from 3.6 ± 1.1 to 65.7 ± 16.2 μg/dl and total serum B12 values decreased significantly (P < 0.005) from 482 ± 56 to 267 ± 42 pg/ml, three hours after SNP therapy. Plasma thiocyanate did not change. Cyanide released from SNP converts hydroxo-cobalamin to cyanocobalamin, which is readily excreted in urine. These variables were not changed in six patients (control) who received trimethaphan. In vitro experiments revealed that none of the serum factor(s) nor nitroprusside interfered with the assay of B12. Hydroxocobalamin may be an appropriate adjunct during SNP therapy.

A randomized comparison of labetalol and nitroprusside for induced hypotension

In a randomized study, labetalol-induced hypotension and nitroprusside-induced hypotension were compared in 20 patients (10 in each group) scheduled for major orthopedic procedures. Each patient was subjected to an identical anesthetic protocol and similar drug-induced reductions in mean arterial blood pressure (BP) (50 to 55 mmHg). Nitroprusside infusion was associated with a significant (p less than 0.05) increase in heart rate and cardiac output; rebound hypertension was observed in three patients after discontinuation of nitroprusside. Labetalol administration was not associated with any of these findings. Arterial PO2 decreased in both groups. It was concluded that labetalol offers advantages over nitroprusside.

Quantitative relationships between plasma beta-endorphin immunoactivity and hemodynamic performance in preoperative cardiac surgical patients

&NA; To quantitate the importance of cardiac dysfunction as a stimulus for plasma immunoactive beta‐endorphin (iBE) secretion, we measured iBE and hemodynamic indices in 65 patients prior to anesthetic induction for coronary artery bypass grafting or valve replacement. Linear regression analysis for the group as a whole showed significant correlations between iBE and stroke index (SI), pulmonary artery wedge pressure (PCW), and right atrial pressure (RAP), but not mean arterial pressure (MAP). Two patient subgroups were identified (P < 0.001 by F‐test): those with low SI and high iBE, or those with high SI and low iBE (cutoffs at 40 ml/m2 and 35 pg/ml, respectively). Correlations between hemodynamics and iBE were always stronger within the low‐SI than the high‐SI subgroups. These correlations were greater for patients with coronary artery than with valvular heart disease. Cardiac output (CO) and cardiac index (CI) correlated with iBE in valve‐replacement and coronary‐grafting groups. These findings were not an artifact of impaired iBE clearance due to renal dysfunction. Our results quantitate the importance of hemodynamic dysfunction for iBE secretion, and indicate that this relationship is particularly strong when stroke index declines below 40 ml/m2.

Continuous monitoring of oxygen tension with a transcutaneous sensor during hypotensive anesthesia.

Transcutaneous oxygen tension (TCPo2) is a useful noninvasive technique for monitoring arterial oxygen tension under stable circulatory conditions. This study was undertaken to determine if TCPo2 is also reliable during sodium nitroprusside‐induced hypotension under general anesthesia. Arterial blood gases and TCPo2 were measured prior to inducing hypotension (baseline), at 20‐min intervals during hypotension, and when systemic arterial pressure had returned to within 10% of the control (pre‐hypotension) value. With induced hypotension, Pao2 and TGPo2 decreased significantly (P<0.05), and were well correlated by linear regression (r>0.85); however, regressions were strongly dependent on the individual patient. The mean regression line for all patients as a group was given by TCPo2 = 0.69 Pao2 + 20.7 mmHg (r = 0.93, P<0.01); significantly different regressions were obtained for each patient (P<0.0001). Comparing changes in TCPo2 versus those in Pao2 (relative change from baseline values) did not substantially reduce the variability among patients. It is concluded that TCPo2 reliably reflects changes in arterial oxygen tension during controlled hypotension under general anesthesia, but that a separate calibration of TCPo2 vs. Pao2, obtained prior to inducing hypotension, may be required for each individual patient.