Loading infusion rate

Treatment Loading Dose Continuous Infusion Rate Drug Interactions... 

Initial Loading Dose Initial Infusion Rate... 

Using a simple one-compartment model, the loading dose and the infusion rate required to maintain a constant plasma concentration can be calculated as follows. 

In patients with heart failure, lidocaine s volume of distribution and total body clearance may both be decreased. Thus, both loading and maintenance doses should be decreased. Since these effects counterbalance each other, the half-life may not be increased as much as predicted from clearance changes alone. In patients with liver disease, plasma clearance is markedly reduced and the volume of distribution is often increased the elimination half-life in such cases may be increased threefold or more. In liver disease, the maintenance dose should be decreased, but usual loading doses can be given. Elimination half-life determines the time to steady state. Thus, although steady-state concentrations may be achieved in 8-10 hours in normal patients and patients with heart failure, 24-36 hours may be required in those with liver disease. Drugs that decrease liver blood flow (eg, propranolol, cimetidine) reduce lidocaine clearance and so increase the risk of toxicity unless infusion rates are decreased. With infusions lasting more than 24 hours, clearance falls and plasma concentrations rise. Renal disease has no major effect on lidocaine disposition. 

B. Maintaining the infusion rate, but doubling the loading dose. 

Headache occurred in 25% of all patients who received an infusion of intravenous immunoglobulin, probably related to larger volumes and fluid shifts, protein loads, and infusion rates (54). Intravenous immunoglobulin caused severe headache in 56% of patients without a history of migraine (55). The pathogenesis of this headache is unknown. 

Although refractory GCSE has been treated with a variety of agents, some practitioners have advocated not only that midazolam should be the first-line agent in refractory GCSE but also that it should be the third-line agent in patients unresponsive to lorazepam plus phenytoin. Table 55-4 contains the loading and maintenance doses for adult and pediatric patients. The continuous-infusion rate should be increased every 15 minutes until seizures are controlled. Most patients respond within 65 minutes. 

Hyperglycemia Stress, infection, corticosteroids, pancreatitis, diabetes mellitus, peritoneal dialysis, excessive dextrose administration Decrease dextrose load by decreasing infusion rate or dextrose concentration (may substitute fat calories) administer insulin... 

Other equations describing relationships important for calculation are those used to determine the j loading dose, infusion rate, and maintenance dose. 

Table 7. Theoretical loading doses and infusion rates for intravenous oxime administration... 

A loading dose is not required, and steady-state concentrations generally are achieved within 10 minutes of initiation of the infusion. The rate of infusion required to increase cardiac output typically is 2.5-10 p,g/kg/min higher infusion rates occasionally are required. The rate and duration of the infusion are determined by the clinical and hemodynamic responses of the patient. The onset of effect is rapid. Dobutamine has a tj/2 of -2 minutes the major metabolites are conjugates of dobutamine and 3-0-methyldobutamine. 

Clinically, an intravenous loading dose of 15 to 18 mg/kg is administered over 30 to 60 min (maximum infusion rate 25 to 50 mg/min). In the presence of severe renal insufhciency or decreased cardiac output the dose is empirically decreased to 12 mg/kg. A loading dose may also be determined by Equation 8.3 ... 

A serum concentration measnrement obtained 30 min after the LD, when distribution is complete, can be nsed to assess the need for and size of subsequent loading doses and for gnidance of the continnation therapy. Once a serum concentration of 10 to 15 itg/ml has been achieved by loading doses, a constant intravenous infusion is started. The required infusion rate/ o (in nig/kg/h) can then be determined based on the target steady-state serum concentration Q i rget (in Itg/nil) and the estimated theophylline population clearance Clp p (in 1/kg/h), taking any known confounding factors into account. 

C. The continuous infusion rate after the loading dose is 1-2 mg/min (children >12 years old, 20-30 mcg/kg/min). 

VI. Dosage and method of administration. Obtain serum ethanol levels after the loading dose and frequently during maintenance therapy to ensure a concentration of 100-150 mg/dL (eg, every 1-2 hours until goal achieved, eg, level = 100 mg/dL, or after change in infusion rate and then every 2-4 hours during the... 

A. Parenteral. Administer slowly intravenously (rate < 50 mg/mln children, < 1 mg/kg/min) until seizures are controlled or the loading dose of 10-15 mg/kg is achieved. For status epilepticus, give 15-20 mg/kg IV over 10-15 minutes and not to exceed 100 mg/minute (children have required as much as 30 mg/kg in the first 24 hours to treat status epilepticus). Slow the infusion rate if hypotension develops. Intermittent infusions of 2 mg/kg every 5-15 minutes may diminish the risk of respiratory depression or hypotension. For alcohol withdrawal seizures, initial dose of 260 mg, then 130 mg every 30 minutes until signs of mild intoxication (see below). 

Calculation of the loading dose (DJ necessary to attain the desired plasma concentration instantaneously and the infusion rate (Q) necessary to maintain the plasma concentration at that concentration. 

This may be accomplished by administering a loading intravenous bolus dose (Z>l) concomitant with the commencement of the infusion rate. 

Please consider a rectilinear plot of loading dose (Dl) against infusion rate (Q) (Eq. 10.17). What information can be obtained from the slope of the plot ... 

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