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High survival rate of hamsters given intratracheal instillations of benzo[a]pyrene and ferric oxide and kept on a high beta-carotene diet.

The study described in this paper was primarily conducted to identify the cell types involved in the formation, progression and regression of metaplastic changes in the respiratory tract epithelium of hamsters after intratracheal intubations with benzo[a]pyrene. Furthermore, the role of vitamin A and beta-carotene in these processes was studied. In the course of the study a remarkable effect of dietary beta-carotene on survival of hamsters became a subject of investigation. Hamsters were fed diets with various levels of vitamin A or beta-carotene and were treated intratracheally with a suspension of benzo[a]pyrene with ferric oxide in saline. The tumour response of the respiratory tract was very low (2.8%) and hyper- and metaplasia of respiratory epithelium were virtually absent. However, an interesting observation was an exceptionally low mortality of only 2% after 69 weeks in the group of hamsters fed a high beta-carotene diet (1% w/w), whereas in the other groups mortality after 69 weeks amounted to 25%. Although the exact cause of death of most of the hamsters could not be established, a 40% reduction of lipid peroxidation in the livers was found in the high beta-carotene group. Moreover, in this group the degree and incidence of nephrosis and of focal mineralization of kidneys and heart were lower than in the other groups. These favourable effects of the high beta-carotene diet may have contributed to the unusually high survival rate in hamsters fed this diet. Further studies are planned to verify and study this observation.

Animals↗

Iatrogenic ruptures of the tracheobronchial tree.

We did a retrospective study in 12 patients with iatrogenic tracheal or tracheobronchial ruptures treated since 1975. Ten female subjects, one male subject, and one child (age range, 8 to 72 years), all of whom had undergone intratracheal intubation, were admitted to the hospital. Four patients had been intubated with a double-lumen catheter (two Carlens type with carinal spur, two Robertshaw without spur), and seven had had "high volume-low pressure" tubes, placed under emergency conditions in three of those seven cases. In one further case, an unsuccessful attempt of percutaneous tracheostomy had been made. The localization of the ruptures (all of them longitudinally in the membranaceous wall; length, 2 to 13 cm; mean, 7 cm) comprised both cervical and intrathoracic trachea in seven, the intrathoracic trachea in three instances, and the left main stem bronchus in two cases. Ten patients had mediastinal and subcutaneous emphysema, seven presented with a pneumothorax, and nine had intratracheal bleeding. The interval until the onset of symptoms and diagnoses differed widely: twice diagnoses were made intraoperatively, during thoracic surgery. The longest interval until diagnosis was 5 days; only then did the patient show subcutaneous emphysema and have retrosternal pain. All patients had surgical repair. Nine recovered without sequelae, and three died of septic multiorgan failure.

Adult↗

Nitrous oxide analgesia for intubating preterm neonates: a pilot study.

AIM: To evaluate the administration of an equimolar mixture of N2O and O2 for intratracheal intubation in preterm neonates with respiratory distress syndrome (RDS). DESIGN: Prospective evaluation of N2O/O2 in premature neonates with RDS. SETTING: Tertiary neonatal unit from March to August 2003. PATIENTS: Twenty-six of 79 neonates admitted for RDS within 48 h of birth. INTERVENTION: N2O/O2 was administered until muscle tone was suppressed. Surfactant was given intratracheally. Patients were extubated as soon as possible. MAIN OUTCOME MEASURES: The time needed for N2O/O2 to suppress muscle tone, an evaluation of sedation/analgesia through movements of the limbs, and indicators of stress-related haemodynamic change, all recorded by an independent observer. RESULTS: In the 26 patients, gestational age was 30.5 (25th, 75th percentile: 30, 32) wk and median body weight was 1540 (1220, 1900) g. Postnatal age at intubation was 2 (2, 3) h. N2O/O2 administration time was 8 (6, 10) min (range 4-15 min). Sedation/analgesia was complete in 77% of patients. No significant differences between pre-procedure and post-procedure values were found for heart rate (p=0.29) or mean arterial blood pressure (p=0.13) (paired Wilcoxon test). Time needed for intubation was 30 (20, 37) s (range 10-60 s). Side effects included transient agitation (3/26) and retching (2/26). Extubation occurred 5 (5, 10) min (range 2-15 min) after surfactant instillation. Apnoeas occurred in 3/26 patients within 2 h after extubation. Two patients required reintubation to repeat surfactant administration within 24 h after extubation. CONCLUSION: N2O/O2 may be helpful for intubation in preterm neonates. Larger randomized, double-blind studies are needed for a thorough evaluation of effectiveness and safety.

Analgesics, Non-Narcotic↗

In vivo gene delivery to the lung using polyethylenimine and fractured polyamidoamine dendrimers.

BACKGROUND: Gene transfer into the airways could be of importance for the treatment of chronic lung diseases such as cystic fibrosis. In the past few years several attempts have been made to effectively deliver DNA to the lung using different viral and non-viral vector systems. Viral vectors and cationic lipids have been tested intensively but the properties of cationic polymers such as polyethylenimine (PEI) 25 kDa and fractured polyamidoamine dendrimers to deliver DNA to the airways have not been studied. Surfactant preparations have been shown to influence pulmonary adenoviral and naked plasmid DNA mediated gene transfer in vivo. We investigated the gene delivery efficiency of branched PEI 25 kDa and fractured dendrimers to the murine lung in vivo and also examined the effect of surfactant on PEI 25 kDa mediated gene transfer to the lung. METHODS: Cationic polymer/DNA complexes were prepared in 25 mM HEPES buffer (pH = 7.4) or double distilled water and administered to the lungs of BALB/c mice via cannula intubation. The trachea, left and right lung, heart, liver and esophagus were examined for luciferase activity. Inflammation was assessed by performing standard histology. RESULTS: PEI/DNA complexes showed a high level of luciferase gene expression in the lung. Complexes formed in double distilled water exhibited higher gene expression than complexes formed in 25 mM HEPES buffer (pH 7.4). The optimal N/P ratio was found to be N/P = 10 in double distilled water. Luciferase activity was only detected in the lung and decreased rapidly in a time-dependent manner. The addition of a natural surfactant preparation, Alveofact, slightly reduced gene transfer of branched PEI 25 kDa. Luciferase gene expression obtained by using fractured dendrimers was very low. CONCLUSION: The present study demonstrates that PEI 25 kDa, but not polyamidoamine dendrimers, effectively mediates transient gene transfer to the murine lung after intratracheal intubation. In conclusion, branched PEI 25 kDa was found to be an effective vector for pulmonary gene delivery in vivo, being superior to fractured dendrimers.

Animals↗

[The determination of the earliest signs of cell damage after translaryngeal intratracheal long-term intubation in rabbits. A light- and electron-microscopic study].

Eighteen New Zealand rabbits were artificially respired, orotracheally with a cuff pressure of approximately 35 mm Hg, for between 2 and 36 h. After 2 h artificial respiration cell degeneration was seen in the area of the cuff, above the cartilage rings, in the form of cytoplasmic degeneration. After a 4 h intubation period an epithelial loss was seen. The basal membrane was intact. A connective tissue oedema, which was limited to the region of the epithelial lesion, became more wide-spread over the 36 h of intubation. A well-developed ulcer could be identified under the light microscope after 36 h. Increased mucous production as well as an increase in bacteria could be observed after 4 h. At no time could a degeneration of the cartilage be seen in the electron micrographs. The intercartilaginous area also remained free from cell degeneration although signs of vascular congestion could be seen.

Animals↗

Meconium stained amniotic fluid: antenatal, intrapartum and neonatal attributes.

OBJECTIVES: To find out the incidence, outcome as well as antenatal, intrapartum and neonatal attributes of meconium stained amniotic fluid (MSAF). DESIGN: Prospective study. SETTING: Neonatal Unit of Hospital. SUBJECTS: 1426 live births occurring in 1500 consecutive deliveries, over one year period. INTERVENTIONS: In all babies born through MSAF, thorough oropharyngeal suction as soon as the head was delivered followed by immediate intratracheal intubation and suctioning in infants depressed at birth. RESULTS: 204 (14.3%) deliveries had MSAF of which thick meconium was present in 141. Hepatitis in mother, fetal distress during labor and intrauterine growth retardation were significant factors associated with MSAF. One fifth of babies born through MSAF suffered severe birth anoxia compared to 5.6% in non-MSAF group. The consistency of meconium had direct bearing on the neonatal outcome. Severe birth asphyxia (SBA) occurred in 27.0 and 6.3% of babies with thick and thin meconium staining, respectively. Meconium aspiration syndrome was observed in 9 babies of thick meconium group and 8 of these were depressed at birth. All deaths occurred in thick meconium group and were associated with SBA. CONCLUSIONS: Selective approach can be adopted for babies with MSAF reserving intratracheal suctioning at birth for depressed neonate or evidence of fetal distress in utero. Rest of the neonates only need careful observation after thorough oronasopharyngeal suctioning.

Amniotic Fluid↗

Treatment of sulfur mustard (HD)-induced lung injury.

An in vivo sulfur mustard (HD) vapor exposure model followed by bronchoalveolar lavage was developed previously in this laboratory to study biochemical indicators of HD-induced lung injury. This model was used to test two treatment compounds--niacinamide (NIA) and N-acetyl cysteine (NAC)--for their ability to ameliorate HD-induced biochemical changes. Anesthetized rats were intratracheally intubated and exposed to 0.35 mg of HD in 0.1 ml of ethanol or ethanol alone for 50 min. At the beginning of the exposure (t = 0), the rats were treated with either NIA (750 mg kg(-1)) or NAC (816 mg kg(-1)), i.p. At 24 h post-exposure, rats were euthanized and the lungs were lavaged with saline (three 5-ml washes). One milliliter of the recovered lavage fluid was analyzed for cellular components. The remaining fluid was centrifuged (10 min at 300 g) and the supernatant was assayed on a Cobas FARA clinical analyzer for lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), albumin (ALB), total protein (TP) and glutathione peroxidase (GP). The HD alone and HD+NIA treatment caused significant increases in all of the biochemical parameters compared with control levels. The NAC treatment yielded LDH, ALB and TP values that, although elevated, were not significantly different from the control. The GP levels were significantly higher than the control but significantly lower than the HD alone levels, indicating some protection compared with the HD alone group. The GGT levels were unaffected by NAC compared with HD alone. Cytological analysis of lavage fluid showed that the percentages of neutrophils were 5.3 +/- 1.0 (mean +/- SEM) for control, 46.6 +/- 4.5 for HD, 31.4 +/- 4.7 for HD + NIA and 21.6 +/- 4.7 for HD + NAC, respectively. The neutrophil counts were significantly higher for the three HD-exposed groups vs controls; however, the NAC-treated group had neutrophil counts lower than HD alone, indicating decreased inflammatory response. These results show that NAC may be useful as a potential treatment compound for HD-induced lung injury.

Acetylcysteine↗

Current concepts in SARS treatment.

The outbreak of severe acute respiratory syndrome (SARS) has drawn enormous attention and caused fear worldwide since early 2003. The disease appears to be under control now; however, the possible return of SARS must be emphasized. Although many clinical experiments have been reported, the treatment of SARS is largely anecdotal, and so far no treatment consensus has been reached. We summarize 14 clinical reports and attempt to assess the effectiveness of various treatment regimens. A combination treatment of steroids and ribavirin was widely used empirically from the outset of the epidemic. In general, the use of steroids for SARS seemed beneficial, but the optimal timing, dosage, and duration of treatment have not yet been determined. On the other hand, ribavirin administration apparently reduced neither the rate of intratracheal intubation nor that of mortality. Moreover, significant toxicity, such as hemolytic anemia, has been attributed to ribavirin. A few preliminary trials and in vitro data suggest the possibility of treating SARS with interferon. Other agents, including the HIV protease inhibitor glycyrrhizin and convalescent plasma, remain to be evaluated.

Antiviral Agents↗