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Relationships among duration of infusion, dose, dosing interval, and steady-state plasma concentrations during intermittent intravenous infusions: studies with metronidazole.

Relationships among duration of infusion (T), dose, dosing interval (tau), maximum and minimum plasma drug concentrations at steady state (Cmax,ss and Cmin,ss, respectively), and the duration of effective plasma concentrations (tD) during multidose intermittent infusion regimens were studied by computer simulation using metronidazole as a model drug. Pharmacokinetic parameter values for metronidazole were obtained from the literature and the minimum effective plasma concentration (MEC) was taken as 6.0 micrograms/ml. Increasing the infusion period of the dose reduces Cmax,ss, but increases Cmin,ss. If intermittent bolus injection of a given dose of drug results in effective plasma concentrations for the entire dosage interval (i.e., Cmin,ss,bolus greater than MEC), then infusion of that dose over any period (T less than or equal to tau) will also result in effective concentrations for the entire dosage interval. However, if the dosage is such that Cmin,ss,bolus less than MEC, the relationships among duration of infusion, dose, dosage interval, and duration of effective plasma concentrations are complex. Therefore a nomogram was developed to allow selection of dose, dosing interval, and infusion period such that Cmax,ss and Cmin,ss could be maintained within a desired range.

Humans↗

Experimental infusion thrombophlebitis. Importance of the infusion rate.

The importance of the method of administration of acid glucose infusions for the venous inflammatory response has been investigated in two series of experimental trials. 60 ml of 5% glucose solution was administered into rabbit-ear veins in three ways: 1) continuously over 5 hours (slow infusion), 2) continuously over 1 hour (rapid infusion), 3) discontinuously during 2 X 30 minutes with an interval of 4 hours (discontinuous infusion). Microscopical examination of the veins revealed that the inflammatory changes were less pronounced after rapid and discontinuous infusions than after slow infusions.

Animals↗

Therapeutic efficacy of multimodal combination therapy using transcatheter arterial infusion of epirubicin and cisplatin, systemic infusion of 5-fluorouracil, and additional percutaneous ethanol injection for unresectable hepatocellular carcinoma.

PURPOSE: Previous studies have shown that a treatment regimen using epirubicin, cisplatin, and 5-fluorouracil (5-FU) (ECF) has a survival benefit for gastric cancer patients. Based on these results and the hypothesis that a combination modality has a better therapeutic advantage over a single mode of therapy, the efficacy of multimodal combination therapy using a transarterial infusion of epirubicin and cisplatin, systemic infusion of 5-FU, and additional percutaneous ethanol injection (PEI) for unresectable hepatocellular carcinoma (HCC) was investigated in this study in comparison with conventional transarterial chemoembolization (TACE). PATIENTS AND METHODS: From July 1997 to September 1998, a total of 52 patients with unresectable HCC who underwent at least two cycles of transarterial chemotherapy were enrolled in this study. Among the 52 patients, 30 (ECF group) received a multimodal combination therapy comprising transarterial infusion of epirubicin (50 mg/m2) and cisplatin(60 mg/m2), systemic infusion of 5-FU (200 mg/m2), and additional PEI every 4 weeks, and the remaining 22(ADR group) received conventional TACE using Adriamycin (ADR, 50 mg) and Gelfoam every 8 weeks. RESULTS: During the follow-up period (mean 13.8 +/ -8.5 months), the objective tumor response of the ECF group was significantly higher than that of the ADR group (53.3 vs 22.7%, P=0.044). The median survival time was 13.5 months for the ECF group and 10.5 months for the ADR group (P=0.026). The cumulative survival rates at 6, 12, 18, and 24 months,respectively, were 90, 57, 27, and 17% for the ECF group and 73, 37, 7, and 0% for the ADR group. Uni-variate analysis showed five prognostic factors including tumor number, tumor morphology, portal vein thrombosis, Child-Pugh classification, and tumor response. With multivariate analysis, portal vein thrombosis and tumor response were identified as the two independent f actors for survival. No serious adverse effect was observed in the ECF group, while there was a higher tendency for hepatic complications in the ADR group. CONCLUSIONS: Combination therapy comprising transarterial infusion of epirubicin and cisplatin, systemic infusion of 5-FU, and additional PEI appears to be feasible and promising as a multimodal approach for unresectable HCC. Furthermore, it may provide a survival benefit for patients with more advanced disease.

Administration, Cutaneous↗

Potentiation of the cytostatic effect of melphalan on colorectal cancer hepatic metastases by infusion of buthionine sulfoximine (BSO) in the rat: enhanced tumor glutathione depletion by infusion of BSO in the hepatic artery.

PURPOSE: Glutathione (GSH) plays an important role in the resistance of tumors to cytostatics. Therefore, depletion of GSH by the GSH synthesis inhibitor buthionine sulfoximine (BSO) has been proposed to enhance the efficacy of certain anticancer agents. We studied the effect of BSO in rats bearing intrahepatically implanted tumors of the CC531 colorectal cancer cell line on the antitumor activity of melphalan (L-PAM). Since these liver tumors tend to derive most of their blood supply from the hepatic artery, we evaluated whether delivery of BSO into the hepatic artery would more selectively decrease GSH levels in the implanted tumor tissue as compared with normal liver and extrahepatic tissues. METHODS: Tumor-bearing rats were treated with a 24-h continuous infusion of 0.375 mmol/ kg BSO via the jugular vein, immediately followed by a bolus L-PAM (15 micromol/kg; 4.5 mg/kg) infusion via the hepatic artery. Laparotomy was performed on day 14 and 28 after treatment for measurement of the liver tumors. For the evaluation of locoregional administration of BSO, a 24-h continuous infusion of 0.375 mmol/kg BSO was delivered into either the hepatic artery, the portal vein, or the jugular vein in freely moving rats and GSH levels in the tumor, liver, kidney, lung, heart, bone marrow, and blood were measured. RESULTS: BSO infusion via the jugular vein increased the antitumor efficacy of L-PAM injected into the hepatic artery 2-fold as determined at 14 days after treatment. Although infusion of BSO via the hepatic artery depleted GSH more severely in the tumor as compared with jugular vein or portal vein administration, the additional effect was only slight (10%). No difference was observed in any other tissue. CONCLUSION: GSH depletion increased the cytostatic efficacy of L-PAM 2-fold in vivo as determined at 14 days after treatment. Hepatic artery infusion of BSO translated into a statistically significant, but probably not therapeutically relevant, increase in tumor GSH depletion as compared with the other routes of BSO administration.

Animals↗

Effects of continuous infusions (10 days) and cessation of infusions of clonidine and rilmenidine (S 3341) on cardiovascular and behavioral parameters of spontaneously hypertensive rats.

Clonidine is a centrally acting antihypertensive drug that acts in vivo at both alpha 1- and alpha 2-adrenoceptor sites, whereas rilmenidine (S 3341) is more selective for alpha 2 adrenoceptors. The present study compared the effects of continuous 10-day infusions of clonidine (5 micrograms/kg/hour) with those of rilmenidine (100 micrograms/kg/hour) on various cardiovascular and behavioral parameters in the spontaneously hypertensive rat. The changes in these parameters after cessation of the infusions were also compared. At these rates of infusion, clonidine and rilmenidine produced quantitatively similar reductions in mean arterial pressure (MAP), lability of MAP and cardiovascular responsiveness during normal behaviors such as eating and grooming. Neither drug infusion affected heart rate. The cessation of the clonidine infusion resulted in a "withdrawal" syndrome characterized by prominent rapid eye movement-sleep rebound, and cardiovascular and behavioral disturbances including an increased lability of MAP, exaggerated cardiovascular responses during normal behaviors, tachycardia, and an "opiate abstinence-like" syndrome including head and body shakes. Cessation of rilmenidine infusion resulted in somewhat similar cardiovascular and behavioral disturbances, but unlike clonidine there was a return to normal rapid eye movement sleep without rebound.

Adrenergic alpha-Agonists↗

New superselective intra-arterial infusion via superficial temporal artery for cancer of the tongue and tumour tissue platinum concentration after carboplatin (CBDCA) infusion.

We developed a new technique of superselective intra-arterial chemotherapy for tongue cancer using a modified (1.35 mm) angiographic catheter. The catheter was confirmed to be inserted into the lingual artery by the new technique. We measured the platinum concentrations in resected tumour tissues after infusion of carboplatin (CBDCA) at 20 mg/m2 over 30 min from 30 min before tumour resection in 12 patients with cancer of the tongue (6 patients: superselective intra-arterial infusion; 6 patients: conventional intra-arterial infusion). The mean platinum concentration in tumour tissue was 10.5 +/- 1.2 micrograms/g wet, which was more than twice higher than, and significantly different from, 4.3 +/- 3.8 micrograms/g wet by the conventional intra-arterial infusion method. This new superselective intra-arterial infusion method allows direct infusion of the anticancer agent into the artery supplying the tumour and is expected to become a new therapeutic modality for cancer of the tongue.

Antineoplastic Agents↗

An in vitro evaluation of flow from multihole epidural catheters during continuous infusion with four different infusion pumps.

We have observed in vitro the distribution of flow from 10 identical multihole epidural catheters during continuous infusion with four different infusion pumps. The pumps chosen were the B Braun Perfusor Secura FT syringe driver and three volumetric infusion pumps utilising different pumping mechanisms (Dekra 3000 BL, Graseby 500 and CADD-Prizm). These pumps infused 0.9% saline through each catheter at 5 ml.h-1, 15 ml.h-1, 50 ml.h-1 and 99 ml.h-1 for 3 min. The number of holes through which flow occurred and the catheter hole where flow predominated during each test were recorded. The pressure waveform generated during each infusion was displayed and the peak pressure recorded. In 38 of the 160 tests (24%) the largest proportion of flow was seen at the hole closest to the catheter tip. The CADD pump generated multihole flow during significantly more tests (p < 0.0001) than the other pumps and produced significantly higher driving pressures (p < 0.001) at all infusion rates compared with the Graseby and Perfusor pumps. The CADD was the only pump to produce flow from all three holes of the catheter at 5 ml.h-1.

Anesthesia, Epidural↗

Rapid fluid infusion therapy decreases the plasma concentration of continuously infused propofol.

BACKGROUND: Rapid fluid infusion therapy to treat hypovolemia in anesthetized patients is a common practical regimen in daily clinical settings. This study investigated the effect of large volume loading on the plasma concentration of propofol (Cp), hemodynamic parameters, hemoglobin concentration (Hb), hematocrit value (Ht) and the bispectral index (BIS). METHODS: Sixty patients were administered propofol using a target-controlled infusion technique. We studied two independent groups. Half of the patients (group F, n = 30) were administered fentanyl, and the other half (group E, n = 30) epidural administration of mepivacaine for analgesia. After achieving a pseudo-steady state of propofol anesthesia, baseline values of blood pressure, heart rate, Hb, Ht, cardiac output, Cp and BIS were measured, and 10 ml/kg Ringer's solution was infused over 15 min. RESULTS: In group F, Cp was significantly decreased from 2.24 (0.69) [mean (SD)] to 2.07 (0.61) microg/ml and in group E from 2.02 (0.98) to 1.75 (0.51) microg/ml immediately after infusion (P < 0.05). The significant reduction lasted until 30 min in group F, whereas, Cp quickly recovered in group E. Cardiac output was increased only in group F. The dilution ratio demonstrated the prolonged diluting effect in group E and the significant correlation with the rate of decrease in Cp (P < 0.0003, R = 0.21). The BIS value showed no significant change immediately after infusion. CONCLUSION: Large volume loading decreased Cp without a significant change in BIS values. The effect of infusion therapy on the depth of anesthesia might be small and usually negligible during propofol anesthesia.

Adolescent↗

Function of isolated hearts from septic, saline-infused, and septic, alcohol-infused rats.

The aim of the present study was to determine whether hearts that demonstrate depressed myocardial reserves as a result of sustained hypermetabolic sepsis would show a potentiation of the dysfunction after an infusion of high doses of alcohol. We have previously shown that myocardial depression is present in hearts removed from hypermetabolic septic rats. Acute alcohol administration has also been shown to have a negative inotropic effect on the heart. In this study, myocardial function was assessed under in vitro conditions in which preload could be varied and aortic outflow resistance controlled and thus heart function could be determined under both low and high workloads. The alcohol-infused group increased cardiac performance as a function of increasing preload similarly to the controls. Heart rate, however, was significantly elevated compared with control. Isolated hearts from septic, saline-infused animals showed depressed cardiac performance both in terms of stroke volume and myocardial work over a range of preloads. The septic, alcohol-infused animals did not show this depression. Thus, a loss of myocardial reserve was demonstrable in hearts isolated from septic, saline-infused rats but not in septic, alcohol-infused rats. Alcohol, at least acutely, seemed to reverse or ameliorate the loss of myocardial reserve induced by sepsis possibly by increasing the ability of the heart to fill during diastole and thus perform volume work.

Animals↗

Long-term hepatic arterial infusion of 5-fluorodeoxyuridine for liver metastases using an implantable infusion pump.

Twenty-one patients with liver metastases of various histologies (predominantly colorectal carcinoma) underwent Infusaid pump implantation for long-term hepatic arterial 5-fluorodeoxyuridine (5-FUdR) infusion. Patients received 5-FUdR infusion on a 2-wk cycle alternating with a 2-wk saline--heparin infusion. A dosage of 0.2-0.3 mg/kg/day (average 0.23 mg/kg/day) was infused for a cumulative 5-FUdR administration of 1940 days. Six patients (29%) responded to therapy (five colorectal, one carcinoid); median response duration was 6 mo. Median survival for the treated group was 17 mo from diagnosis of liver metastases and 13 mo from pump implantation. Median survival among the six responding patients was 15 mo from diagnosis of liver metastases and 11 mo from pump implantation. Comparison of survival from the diagnosis of liver metastases of the treated group to ten patients found ineligible for the study by virtue of extrahepatic metastases revealed no significant difference in median (18 mo for ineligible group) or overall survival. However, median survival for the treated group after pump implantation (13 mo) was significantly better than the median survival of the ineligible group after evaluation for this study (4 mo). Toxicities of therapy included fatigue, anorexia, nausea, vomiting, toxic hepatitis, epigastric pain, and diarrhea. No patients died of toxicity, but six patients required hospitalization for management of pain or vomiting. No serious technical complications developed in any patient except separation of the infusion catheter at its junction with the pump in one patient, necessitating pump replacement for continuation of therapy. These survival data suggest identification of new anticancer agents for hepatic arterial infusion.

Adult↗

[Brain injury induced by continuous infusion of endotoxin (ET) in rat--relationship between ET infusion hours and development of cerebral and visceral lesions].

Experimental generalized Shwartzman reaction (GSR) in animals can be induced by systemic injection of bacterial endotoxin lipopolysaccharide (ET) and presents with thrombotic occlusions of small blood vessels in different organs analogous to disseminated intravascular coagulation (DIC) in man. It is known that DIC involvement of the central nervous system (CNS) in man presents with grave prognosis, but there is a paucity of information concerning CNS involvement in animals with ET induced GSR. In order to better understand the pathogenesis of CNS involvement of DIC in man, and to search for better prophylactic and therapeutic measures against DIC, animal model of DIC was induced by continuous intravenous infusion of E coli ET. A total of 56 male Donryu rats were divided into 6 groups and infused with physiologic saline (controls) and ET lipopolysaccharide at 88.5 micrograms/hour. The rats were killed at 6 different intervals from 24 to 160 hours and examined postmortem. Intracerebral hemorrhagic lesions were seen in 2 of 7 rats (29%) as early as 24 hours of ET-infusion and increased to 77% to 87% of rats receiving continuous ET infusion up to 160 hours. Formation of fibrin thrombi was uncommon in intracerebral blood vessels, but it was frequently observed in choroid plexus capillaries. Fibrin thrombi in other viscera (heart, lungs, liver, kidneys, spleen) were common but decreased toward the end of 160-hour infusion period. Results of this study showed that a continuous intravenous infusion of large dose ET lipopolysaccharide in rats produces intracerebral hemorrhagic lesions analogous to DIC changes of brain seen in man.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Intraarterial urokinase infusion therapy for arterial occlusive disease of the pelvis and extremities with special reference to short-term high dose infusion].

Thirty-five complete arterial occlusions of pelvis and extremity in 29 patients were treated with intraarterial urokinase infusion therapy. In 28 limbs, the occlusions were due to arteriosclerotic change and in 7 lesions, the occlusions were due to Burger's disease. The patients with arteriosclerotic change ranged in age from 52 to 84 years with a mean age of 68 years, and the patients with Burger's disease ranged in age from 35 to 47 years with a mean age of 43 years. There were 24 men and 5 women. The estimated duration of the occlusion was from 5 days to 5 years with a mean duration of 11 months. The length of the occluded segments ranged from 1 to 45 cm with a mean length of 13.9 cm. The occlusion was located in the iliac artery in 13 patients, the femoral artery in 11 patients, both the iliac and the femoral artery in 2 patients, the popliteal artery in 5 patients, the femoro-popliteal artery in 1 patient, the brachial artery in 2 patients and the radial artery in 1 patient. The infusion catheter was gently advanced into the proximal portion of the clot over a flexible guide wire, and urokinase was infused at a rate of 5000-10000 IU/min, as a short term high dose infusion (SHI), until antegrade blood flow was reestablished. The catheter was then withdrawn to a point proximal to all of the remaining clot, and the infusion rate was reduced to 10000-20000 IU/h as a continuous low dose infusion (CLI). After thrombolytic recanalization, a percutaneous transluminal angioplasty (PTA) was performed in those cases which demonstrated a residual narrowing of the lumen. The initial success rate was 86%. Reocclusions were observed in 5 lesions (17%) and a second recanalization was successful in 2 of 3 patients. The 1-year cumulative patency rate following recanalization was 88.4% and the 2-year patency rate was 78.6%. No significant complications directly related to the procedure were observed. SHI combined with CLI and PTA appears to be an effective and safe therapy for chronic long segmental arterial occlusion.

Adult↗

The use of a volumetric infusion pump for the intra-arterial infusion of drugs.

Volumetric infusion pumps are widely used for intravenous infusions. We have extended their use to the intra-arterial infusion of drugs. An in vitro evaluation of the performance of such devices, under experimental conditions comparable to an intra-arterial infusion, was carried out. The results obtained confirmed the accuracy of volumetric infusion pumps for intra-arterial infusions. The system was found to be safe, reliable and simple in clinical practice.

Humans↗

[Infusion kinetics of drugs injected into the drip chamber of an infusion set].

The infusion kinetics of drugs injected into the "drip-chamber" of an i.v. infusion set has never been studied, although this route of drug administration is used more and more frequently in hospitalized patients. The drug is eliminated from this "drip-chamber" and hence infused into the body by 1.-order kinetics. A half-life of administration can be calculated and experimentally verified. This t 1/2 is equal to the ratio of the volume of infusion fluid in the "drip-chamber" (which can be estimated) and the infusion velocity of the i.v. drip (which is chosen) with the ln 2 as the proportionality constant. Hence the velocity of administration of the drug is not constant. Just after the injection more of the drug reaches the body per unit time than later on. This type of drug administration should therefore not be used if high plasma concentrations at the beginning are to be avoided or a constant infusion is desired.

Infusions, Parenteral↗

[Brain SPECT by intraarterial infusion of 99mTc-HMPAO for assessing the cerebral distribution of carotid artery infusions in patients with brain tumor].

In order to assess the cerebral distribution of intracarotid chemotherapy, 17 postoperative patients with brain tumor underwent brain SPECT obtained by intraarterial infusion of 18.5 MBq of 99mTc-HMPAO. Injection methods were continuous (5.0 ml/min) or pulsatile infusion with supraor infraophthalmic catheterization. The findings obtained by brain SPECT were frequently different from those of angiography and/or DSA. In supraophthalmic catheterization with continuous infusion, only 2 of 10 studies (20%) had homogeneous distribution and 5 of them (50%) had maldistribution of 99mTc-HMPAO which appears in association with laminar flow effect. The remaining 3 studies showed localized distribution (two: tumor localization, one: healthy brain localization). On the other hand, all of 5 studies with pulsatile infusion had homogeneous distribution of 99mTc-HMPAO. In infraophthalmic catheterization, all but one of 5 studies had homogeneous distribution with continuous infusion. These results suggest that pulsatile infusion may be effective in eliminating maldistribution of 99mTc-HMPAO in supraophthalmic catheterization. In conclusion, we are convinced that 99mTc-HMPAO is a useful intraarterial agent for assessing cerebral distribution of intracarotid chemotherapy.

Adolescent↗

Norepinephrine infusion following cardiopulmonary bypass: effect of infusion site.

The placement of left atrial catheters following cardiopulmonary bypass (CPB) allows accurate monitoring of left ventricular filling pressures, as well as access for the infusion of vasoactive drugs. While the left atrial administration of norepinephrine (NE) is thought to provide higher systemic arterial NE levels while minimizing any pulmonary vasoconstriction, no study critically compares central venous and left atrial NE infusion following cardiopulmonary bypass. A canine model was used to compare central venous and left atrial NE infusion at three dosages (0.2, 0.4, and 0.6 microgram/kg/min) both prior to CPB and following 2 hr of hypothermic CPB at 27 degrees C. Prior to CPB, there was no difference in the hemodynamic efficacy of central venous and left atrial NE infusion at any dosage. The pulmonary circulation metabolized 16-29% of circulating NE. Only at the 0.2 microgram/kg/min dose was there a difference in the arterial NE level between central venous (3474 +/- 486 pg/ml) and left atrial (5504 +/- 751 pg/ml, P = 0.019) NE administration. Above this dose, no difference in the arterial NE level was identified. Following 2 hr of CPB, the pulmonary endothelium metabolized a significantly higher percentage of circulating NE (35-42%). Despite this increased extent of pulmonary metabolism, there was no difference in the hemodynamic efficacy or the resulting arterial NE level of central venous and left atrial NE infusion at a given dose. In conclusion, the results demonstrate: (1) increased pulmonary NE uptake following CPB, and (2) no difference in hemodynamic efficacy between central venous and left atrial NE infusion over a wide range of three doses in a model with normal lungs.

Animals↗

Intraseptal infusions of muscimol impair spontaneous alternation performance: infusions of glucose into the hippocampus, but not the medial septum, reverse the deficit.

As observed with intraseptal injections of opioid receptor agonists, direct infusions of GABAergic receptor agonists into the medial septum impair performance on several tasks that involve spatial or working memory processes in rats. Because the effects of opioid-induced impairments can be reliably reversed by concomitant intraseptal infusions of glucose, the experiments reported here determined whether impairments produced by GABAergic agonists would similarly be reversed by glucose. The findings of Experiment 1 showed, in male Sprague-Dawley rats, that intraseptal infusions of the GABA agonist muscimol (1 or 3 nmol/0.5 microliter) impaired spontaneous alternation performance. The results of Experiment 2 indicated that intraseptal infusions of glucose (8, 17, or 33 nmol) or glutamate (15 or 30 nmol) did not attenuate the muscimol-induced deficit on spontaneous alternation performance, whereas infusions of the GABAergic antagonist bicuculline methiodide (0.1 nmol) did. However, the findings of Experiment 3 indicated that glucose injections (50 nmol/0.5 microliter) into the hippocampus did reverse the impairing effect of the intraseptal muscimol infusions. Combined, these findings suggest that the neurochemical regulation of learning and memory may involve hierarchical interactions between particular neurotransmitter and neuroanatomical systems. Specifically, medial septal GABAergic effects on spontaneous alternation prevail over those of glucose or glutamate in the medial septum, but are overridden by the effects of glucose in the hippocampus.

Animals↗

Comparison of ventricular steady-state infusion with bolus infusion and pressure recording for differentiating between arrested and non-arrested hydrocephalus.

In 6 years 26 adult patients with chronic communicating or non-communicating hydrocephalus underwent ventricular fluid pressure (VFP) recording, including intraventricular steady-state and bolus infusion tests. Patients were treated with a shunt when steady-state infusion yielded a csf outflow resistance (Rcsfs) greater than 10 mm Hg/ml/min; the success rate was 83%. The main purpose of the study was to compare Rcsfs with outflow resistance obtained by bolus infusions (Rcsfb), pressure-volume index (PVI) and VFP. Rcsfs was higher than Rcsfb, particularly when resistance was high and the degree of disturbance of csf dynamics was reflected by Rcsfs better than by Rcsfb. The PVI showed a roughly inverse relationship with the Rcsfs but was not helpful in differentiating arrested from non-arrested hydrocephalus. Rcsfs and VFP correlated better than expected. A high Rcsfs was associated with an elevated VFP and a normal Rcsfs with a normal VFP. VFP only varied when Rcsfs exhibited a mild to moderate increase. It is concluded that steady-state infusion remains the most reliable method for the prediction of the result of shunting. We recommend shunting when Rcsfs is greater than 10 mm Hg/ml/min. Bolus infusions provide valuable data on brain elastance and additional information on csf outflow resistance. VFP recording is certainly worthwhile because infusion tests can be omitted when VFP is clearly elevated and useful information is obtained when Rcsf is borderline.

Adolescent↗