Respiratory parameters

Cardiovascular and respiratory parameters should be monitored continuously (see Table 12-1). Trends, rather than specific CVP or PAOP numbers, should be monitored because of interpatient variability in response. 

The AEGL-1 concentration was based on a 1-hour (h) no-effect concentration of 8,000 parts per million (ppm) in healthy human subjects (Emmen et al. 2000). This concentration was without effects on pulmonary function, respiratory parameters, the eyes (irritation), or the cardiovascular system. Because this concentration is considerably below that causing any adverse effect in animal studies, an intraspecies uncertainty factor (UF) of 1 was applied. The intraspecies UF of 1 is supported by the absence of adverse effects in therapy tests with patients with severe chronic obstructive pulmonary disease and adult and pediatric asthmatics who were tested with metered-dose inhalers containing HFC-134a as the propellant. Because blood concentrations in this study approached equilibrium following 55 minutes (min) of exposure and effects are determined by blood concentrations, the value of 8,000 ppm was made equivalent across all time periods. The AEGL-1 of 8,000 ppm is supported by the absence of adverse effects in experimental animals that inhaled considerably higher concentrations. No adverse effects were observed in rats exposed at 81,000 ppm for 4 h (Silber and Kennedy 1979) or in rats exposed... 

In routine inhalation studies, it is generally accepted that the respiratory parameters are relatively constant when the animals are similar in age, sex, and body weight. This leaves only C and t to be the major variables for dose consideration. 

TABLE 10.1. Respiratory Parameters for Common Experimental Species and Humans... 

While irritancy resulting from the above reflex reaction is one cause of altered respiratory parameters during exposure, there are many others. These include other types of reflex response, such as bronchoconstriction, the narcotic effects of many solvents, the development of toxic signs as exposure progresses, or simply a voluntary reduction in respiratory rate by the test animal due to the unpleasant nature of the inhaled atmosphere. The extent to which these affect breathing patterns and hence inhaled dose can only be assessed by actual measurement. 

The mitochondrial respiratory parameters have also been employed to determine the toxicity of surfactants, including anionic (LAS), nonionic (NPEO) and their metabolites, sulfophenyl carboxylates (SPCs), NP and nonylphenoxy carboxylate (NPECi) [37]. The system employed was the in vitro response of submitochondrial particles from beef heart. The EC50 toxicity calculated as the reduction rate of NAD+ ranged from 0.61 mg L-1 for a commercial LAS mixture to 18 000 mg L-1 for SPCs, and 1.3 mg L-1, 8.2 and 1.8mgL 1 for NPEOio, NPECi and NP, respectively. These results indicate that from the toxicity perspective, LAS is the compound demanding increased attention, while for NPEO, the parental compound and the metabolites must be quantified. 

The following values were used for respiratory parameters in the equation above ... 

Report 30 minutes following the dosing, rats returned to the plethysmographic chamber and respiratory parameters measured continuously for 5 minutes After 1,2, and 4 hours, each animal returned to its designated plethysmographic chamber and respiratory parameters are measured continuously for 5 minutes following a 5-min stabilization period One copy of the draft final report One bound and unbound copy of the final and an electronic copy in Word and PDF... 

Because the safety profiles defined by safety pharmacology studies can have a significant impact on the successful development of new therapeutic agents, it is important that the techniques and assays used in safety pharmacology studies minimize the occurrence of false negative and false positive results. For this reason, techniques that provide direct measures of respiratory parameters should be used. A direct measure is one that provides the endpoint of interest, in contrast to an indirect measure that provides a surrogate endpoint,... 

Glenn (1980) examined the anesthetic activity of propofol (ICI 35868) in mice, rats, rabbits, cats, pigs and monkeys, including cardiovascular and respiratory parameters and EEG studies. 

Schins, R.P., Emmen, H., Hoogendijk, L., Borm, P.J.A. (2000). Nasal inflammatory and respiratory parameters in human volunteers during and after repeated exposure to chlorine. Eur. Respir. J. 16 626-32. 

Frequency, clinical characteristics and respiratory parameters of hepatopulmonary syndrome. Mayo Clin. Proc. 2004 79 42-48... 

Much information can be gained from in-life physiological measurements such as blood pressure, electrocardiograms, body temperature, and respiratory rate. When the number of studies is reduced due to the lack of appropriate species and the potential for development of neutralizing antibodies, as much information as possible should be obtained from the few studies that are conducted. In-life measurements assume more importance in these cases. When the product is likely to contain proteins that may cause acute serum sickness type responses and pyrogens, measurements of blood pressure, body temperature, and respiratory parameters are especially important. 

Wearing respirators affects respiratory parameters, such as ventilatory volumes and tidal... 

A system for study of respiratory reactions was developed in the previously described primate with Ascaris by aerosol challenge that was reproducible CFig. 5) simple to do, and easy to adapt to studying the effects of pharmacologic agents on the respiratory parameters involved in the Ascaris reaction (20). 

FIGURE 65.3 Concurrent typical changes in blood and respiratory parameters during exercise progressing from rest to maximum. (Adapted and redrawn from Skinner, J.S. and McLellan, T.H. 1980, by permission of the American Alliance for Health, Physical Education, Recreation and Dance.)... 

Bassett L, Troncy E, Robichaud A, Schuessler TF, Pouliot M, Ascah A, Authier S (2014) Non-invasive measure of respiratory mechanics and conventional respiratory parameters in conscious large animals by high frequency Airwave Oscillometry. J Pharmacol Toxicol Methods 70(l) 62-65... 

Tmax (Redfern et al. 2011b). For inhalation toxicology studies, simultaneous measurement of respiratory parameters can be achieved using head-out plethysmography (Nirogi et al. 2012). 

Recent technological advances enable measurement of respiratory parameters in dogs using a non-restraint, jacketed telemetry method. This technique is known as respiratory inductive plethysmography (Neumann et al. 1998) and involves the placement of flexible belts around the thorax and abdomen, enabling continuous measurement of respiratory parameters for up to 24 h (Murphy et al. 2010). This noninvasive telemetry technique also enables simultaneous measurement of cardiovascular parameters (Bailey et al. 2012) and can also be adapted to nonhuman primates (Soloviev et al. 2007 Kearney et al. 2011) making it an attractive proposition for inclusion in repeat-dose toxicity studies. 

The addition of ketamine as an opiate sparer, 1.5 or 5 mg per bolus morphine dose, has been studied in 58 patients undergoing transthoracic heart and lung surgery, a procedure that is associated with severe pain [122 ]. Those who took ketamine used 50% less morphine and required less rescue diclofenac for pain control. Pain scores were consistently lower with ketamine, despite reduced amounts of morphine administered. Respiratory parameters were much better with ketamine none compared with seven patients requiring oxygen for hypoxia. The... 

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