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PubMedDate not supplied

Suppression of pentylenetetrazol-elicited seizure activity by intraosseous lorazepam in pigs.

Use of the intraosseous (i.o.) route as an alternative venous access for drug administration has increased. This study examined the efficacy of i.o. lorazepam (LZP) in suppressing pentylenetetrazol (PTZ)-induced seizure activity in pigs. Domestic swine (13-20 kg) were prepared for recordings of arterial blood pressure, EEG, and electrocortical activity. Seizure activity was induced by PTZ (100 mg/kg i.v.). Sixty seconds after onset of seizure activity, animals either received no drug (control) or LZP (1.0 mg/kg) administered i.v. or i.o. via an 18- or 13-gauge spinal needle inserted in the right proximal tibia. Both i.o. and i.v. LZP significantly suppressed the duration of seizure activity (DSA) (s/min interval) within 1 min following drug administration: DSA control, 46.2 +/- 3.6; i.v. LZP, 25.0 +/- 5.1; i.o. (18-gauge) LZP, 27.6 +/- 6.0; i.o. (13-gauge) LZP, 24.0 +/- 2.4. Seizure activity was essentially abolished at 1 min following LZP infusion. In addition, both i.v. and i.o. LZP did not have significant effects on the basal heart rate and mean arterial blood pressure. The data demonstrate that in swine (1) the i.o. route is an effective alternative venous access for LZP administration, and (2) the size of spinal needles does not affect the antiepileptic efficacy of i.o. infusion of LZP.

Animals↗

PubMed1989

Drug therapy of cardiopulmonary resuscitation in children.

In contrast to adults, cardiopulmonary arrest in infants and children is rarely an acute, primary cardiac event. Instead, it is often the terminal event in a progressive deterioration of respiratory or circulatory function. Successful resuscitation from cardiac arrest therefore is unusual in the paediatric patient and most survivors have persistent neurological impairment. Rapid vascular access and recall of drug dosages are major obstacles in treating paediatric emergencies. This paper reviews vascular access and alternative drug delivery methods. The endotracheal and intraosseous routes provide alternative sites for drug delivery, but the optimal doses and methods of drug administration via these routes are unknown. Indeed, although great progress in cardiopulmonary resuscitation (CPR) research has been made over the past 10 years, there are only limited data on paediatric arrest mechanisms and drug treatment. In this paper, recommended dosages and mechanisms of action of drugs useful during cardiopulmonary resuscitation are reviewed, highlighting recent data which suggest that changes in current drug recommendations may be needed. To avoid delays in management, precalculated tables of drugs should be readily available in emergency departments and other care areas where paediatric cases are likely to be seen. Adrenaline (epinephrine) remains the drug of choice in a cardiac arrest, but the most effective dose may be higher than currently used. Treatment of acidosis during the arrest concentrates on restoration of ventilation and blood flow and not on bicarbonate administration. In the post-arrest setting increasing data suggest bicarbonate may not be beneficial and may actually be detrimental. Calcium and atropine also have relatively minor roles in resuscitation pharmacology. Calcium is only indicated to treat hypocalcaemia, counteract the effects of hyperkalaemia or hypermagnesaemia, or reverse calcium channel blocker toxicity. Finally, the role of isoprenaline (isoproterenol), dopamine, dobutamine and adrenaline infusions to restore or maintain cardiovascular stability post-arrest is reviewed.

Child, Preschool↗

PubMed1996

[Intraosseous puncture in preclincal emergency medicine. Experiences of an air rescue service].

UNLABELLED: In prehospital emergency treatment, the timely establishment of a secure vascular access, especially in infants and small children, can be difficult or even impossible. An alternative to the puncture of peripheral or central veins is intraosseous (IO) puncture However, experience with this method in prehospital emergency medicine within the Federal Republic of Germany is extremely limited at present. After intensive theoretical and practical training of our trauma anaesthesiologists, IO puncture was introduced in our rescue helicopter program "Christoph 22" as an alternative to peripheral or central venous puncture in the prehospital treatment of patients up to 6 years of age. IO puncture is indicated after a maximum of three failed peripheral venous puncture attempts. The purpose of this study was to collect data and summarise first-hand experience on the prehospital use of the IO method as well as the practicability of our prescribed IO puncture algorithm in order to subject them to critical review and evaluation. MATERIALS AND METHODS: A restrospective study by the rescue helicopter service "Christoph 22" was carried out for the period 1 June 1993-31 August 1995. RESULTS: In a total of 1,455 primary rescue missions flown, the proportion of patients < and = 6 years of age, was 6.2% (n = 90). Ten patients in this partial collective (11.1%) were subjected to IO puncture (Fig. 3). In all of these cases (10/10), the first IO puncture attempt was successful. A standardized puncture technique was performed using the proximal tibia. The time required to successful placement of the IO infusion line was < and = 60 s in all cases. Complications, especially incorrect needle position, did not occur during the study period. Materials infused by IO infusion before hospitalisation included crystalloids (Lactated Ringer's, Päd OP) as well as colloids (hydroxyethylstarch, human albumin), adrenaline, atropine, ketamine, thiopentone, diazepam, fentanyl, succinylcholine, and vecuronium (Table 3). Prehospital induction of general anaesthesia using the IO infusion line was required by 2/10 children; dosage and onset of administered drugs was described by the trauma anaesthesiologists as being similar to that using an i.v. infusion line. Seven of the patients had been treated prior to the arrival of the rescue helicopter team by other emergency medical personnel; in all of these cases multiple peripheral and in 3 additional central venous puncture attempts had failed (duration of attempts: 10-50 min). Upon arrival of the rescue helicopter, 5 of these patients had been pulseless and non-breathing (Table 2). CONCLUSION: The IO infusion technique has proven to be a simple, fast, and safe alternative method of emergent access to the vascular system.

Aircraft↗

PubMed2006

Inhibition of human prostate cancer growth, osteolysis and angiogenesis in a bone metastasis model by a novel mechanism-based selective gelatinase inhibitor.

Metastasis to the bone is a major clinical complication in patients with prostate cancer (PC). However, therapeutic options for treatment of PC bone metastasis are limited. Gelatinases are members of the matrix metalloproteinase (MMP) family and have been shown to play a key role in PC metastasis. Herein, we investigated the effect of SB-3CT, a covalent mechanism-based MMP inhibitor with high selectivity for gelatinases, in an experimental model of PC bone metastases. Intraperitoneal (i.p.) treatment with SB-3CT (50 mg/kg) inhibited intraosseous growth of human PC3 cells within the marrow of human fetal femur fragments previously implanted in SCID mice, as demonstrated by histomorphometry and Ki-67 immunohistochemistry. The anti-osteolytic effect of SB-3CT was confirmed by radiographic images. Treatment with SB-3CT also reduced intratumoral vascular density and bone degradation in the PC3 bone tumors. A direct inhibition of bone marrow endothelial cell invasion and tubule formation in Matrigel by SB-3CT in vitro was also demonstrated. The use of the highly selective gelatinase inhibitors holds the promise of effective intervention of metastases of PC to the bone.

Animals↗

PubMedDate not supplied

A comparison of intraosseous and intravenous routes of administration for antiseizure agents.

Intravenous (i.v.) access for administration of antiepileptic drugs can be time-consuming and difficult in an infant during a seizure. This study examined the intraosseous (i.o.) route as an alternative means of vascular access for drug administration in an animal-seizure model. Domestic swine (13-20 kg) were anesthetized with ketamine (20 mg/kg i.m.) and alpha-chloralose (80 mg/kg i.v.) and given gallamine (4 mg/kg i.v.) to prevent muscle fasciculations. Tracheosotomies were performed and the animals were ventilated with a Harvard respirator. The left femoral vein was cannulated and pentylenetetrazol (PTZ) (100 mg/kg) was given to elicit epileptogenic activity. Sixty seconds after onset of epileptogenic activity, the animals received saline or diazepam (DZP) (0.1 mg/kg) or propranolol (2.5 mg/kg) i.v. or via the i.o. route (18-gauge spinal needle placed in the right proximal tibia). Both DZP and propranolol were effective in suppressing epileptogenic activity via the i.v. or i.o. routes. Thus, the i.o. route is a rapid and effective alternative route for the administration of antiepileptic drugs when an i.v. route cannot be readily established.

Animals↗

PubMed1991

Intraosseous administration of antibiotics: same-dose comparison with intravenous administration in the weanling pig.

STUDY OBJECTIVES: To assess the reliability of the intraosseous route of administration for delivery of a loading dose of broad-spectrum antibiotics in a pediatric animal model. DESIGN: Serum levels achieved within 90 minutes of equivalent intraosseous (IO) and IV bolus dosing of ceftriaxone, cefotaxime, and a combination of ampicillin and gentamicin were compared in the weanling pig. SUBJECTS: Twelve female weanling pigs were studied in the Animal Facilities Laboratory at the University of Mississippi Medical Center. INTERVENTIONS: Through a proximal tibial IO catheter, each anesthetized animal received one of the following: 50 mg/kg ceftriaxone, 50 mg/kg cefotaxime, or 300 mg/kg ampicillin followed immediately by 2.5 mg/kg gentamicin. Venous blood was obtained for antibiotic assay at 15, 30, 45, 60, and 90 minutes after IO injection. The animals were allowed to recover, and, after a one-week washout period, each received the same antibiotic and dose as before through a peripheral IV. Levels were assayed at the same intervals and IO versus IV were compared. MEASUREMENTS AND MAIN RESULTS: Comparable serum levels of all four antibiotics were achieved by the two routes. Gentamicin levels were statistically indistinguishable IO versus IV at all assay intervals. Ampicillin and cefotaxime levels achieved by the two routes were equivalent within one hour of dosing. Serum levels of ceftriaxone after IO administration paralleled those after IV dosing but remained significantly lower at all time intervals. CONCLUSIONS: In the weanling pig model, the IO route was used to deliver serum levels of broad-spectrum antibiotics comparable to those attained after IV administration. The data support the use of standard parenteral doses for IO administration. To overcome potential avid protein binding of ceftriaxone in the bone marrow, we recommend using ceftriaxone at its highest recommended IO loading dose. Consistent with many other medications that have been similarly tested, these data indicate that initial or empiric antibiotic coverage in hypodynamic and shock states in infants and young children need not await the establishment of traditional IV access.

Ampicillin↗