Perioperative Factors Associated With Puppy Vigor After Delivery by Cesarean Section

Experimental Design

Veterinarians in private practice and teaching hospitals in the United States and Canada were invited to participate in a prospective survey of their canine cesarean sections. Details of enrollment criteria and descriptive statistics of the sample population have been reported.¹² In brief, patients were included in the study once the decision was made for them to undergo a cesarean section, regardless of the reason. Veterinary practitioners had the freedom to use whatever anesthetic protocol they wanted, and they were free to change their protocol at any time, for any reason. After each cesarean section, practitioners returned a survey form to the authors, giving details of the anesthetic technique they had used, the morbidity and mortality rates in dams, and the number of puppies surviving at birth and at 2 hours and 7 days after birth. For the purposes of the survey and to clarify the results section, a “live puppy” was defined as a puppy in which a heartbeat was visualized, palpated, or ausculted. A “decomposed puppy” was defined as a cesarean-born puppy in which fetal mortality was accompanied by obvious signs of decomposition (e.g., the fetus was mummified or putrid, or it had easily epilated hair or shrunken eyes). In other cases, where in utero death had occurred and there were no obvious signs of decomposition, puppies were defined as “freshly dead.” A “deformed puppy” was defined as any puppy with a malformation that was noticeable on superficial physical examination. “Delivery time” was defined as the minutes from induction of anesthesia to delivery of the first puppy. Anesthesia time started at the intubation of bitches receiving general anesthesia or the time of injection of a sedative or tranquilizer for those receiving sedation and a local anesthetic. Under maintenance anesthetic, the category of “injectable anesthetic” included any tranquilizer or anesthetic (except an inhaled anesthetic) that was administered prior to delivery of the puppies. “Spontaneous” breathing, moving, or vocalizing of puppies was defined as occurring within 2 minutes of delivery. Dam head types were categorized as “brachycephalic,” “mesaticephalic,” or “dolichocephalic.”³

Puppy vigor was determined by assessing whether the newborn was spontaneously breathing, moving, or vocalizing within 2 minutes of birth. Earlier analysis indicated increased odds for all puppies in a litter being alive at 2 hours after birth if all puppies in a litter were breathing spontaneously at birth.¹ It also showed increased odds for all puppies in a litter being alive at 7 days if at least one puppy in the litter vocalized spontaneously at birth.¹ These two parameters (i.e., spontaneous breathing and vocalizing), together with spontaneous movement, were used in the current study to describe puppy vigor at delivery.

Screening Tests

Litter was the unit of analysis. The percentage of puppies for each vigor parameter (i.e., breathing, moving, and vocalizing) was calculated for each litter. Following this, screening analyses of the potential explanatory factors were done nonparametrically (the data was skewed) for each vigor parameter.⁴⁵ Initially, 70 potential risk factors were identified from the information on the survey forms [Table 1]. This list did not include individual anesthetics, analgesics, or tranquilizers that were used in <10 cases or in breeds that were represented by <10 cases; these were ignored because the small sample size prevented meaningful analysis. One practice, practice “A,” was included as a variable because it provided 199 (24.7%) litters, and the authors wished to account for this large proportion coming from one practice. The 55 categorical risk factors were tested for an association with each of the three puppy vigor parameters by using Wilcoxon’s rank-sum test (two-sided). The effect of type of practice was also evaluated by comparing teaching institution to private practice. The 15 continuous risk factors were tested for relationships to puppy vigor using two-sided Spearman’s correlations. Factors that were associated with puppy vigor (P≤0.10) were then evaluated for collinearity with the other potential factors that had a P value of ≤0.10. Choices were made (based on missing values and on a priori interest and biological reasoning) among variables if high collinearity was found (i.e., rank correlation of ≥0.08 or significant chi-square [χ²] tests that also had significant cell χ² values).

Modeling

Because the continuous distribution of the outcome variables was extremely skewed, the authors dichotomized them to make them valid for multivariable testing. Hence, after screening and before modeling, puppy-vigor parameters were transformed from continuous data (i.e., percentages) to categorical data that answered the following questions: “Were all puppies in the litter spontaneously breathing at birth?” (yes or no); “Was any puppy in the litter spontaneously vocalizing at birth?” (yes or no); and “Was any puppy in the litter moving spontaneously at birth?” (yes or no). Potential explanatory factors for puppy vigor that passed screening (and were retained after collinearity checks) then underwent a stepwise backward logistic-regression modeling; there was one model for each puppy-vigor characteristic. The odds ratios (OR) and 95% confidence intervals were determined for the factors that passed this modeling (P≤0.10). For each risk factor, the OR were adjusted for all other factors in the appropriate model.

Descriptive Summary

The surgery dates for 807 bitches ranged from December 1994 to May 1997. The descriptive results of this study have been published.¹ However, pertinent information for the current analysis can be summarized here. The cumulative neonatal survival rates at time of delivery, at 2 hours of age, and at 7 days of age were 92%, 87%, and 80%, respectively, for cesarean-born puppies (n=3,410). Emergency surgery accounted for 58% of the cases. For both elective and emergency surgery, the bulldog was the most frequently represented breed. The most common methods of inducing and maintaining anesthesia were to use isoflurane for both induction and maintenance (34%) or propofol induction followed by isoflurane maintenance (30%). The two most common methods of maintaining anesthesia were to administer isoflurane (79%) and to use injectable anesthetics (16%). Dams most commonly received intravenous fluids (53%) for perioperative support.

The overall percentages of live-born puppies that were spontaneously breathing, moving, or vocalizing at birth were 85%, 73%, and 60%, respectively. The percentage of each litter’s live-born puppies that spontaneously breathed, moved, or vocalized is summarized in Table 2. Seven-hundred forty (92%) litters did not have any decomposed puppies, 652 (81%) litters did not have any freshly dead puppies, and 693 (86%) litters did not have any deformed puppies in the litter.

Risk-Factor Analysis

The factors that passed screening and were offered to the models are listed in Table 3. The adjusted OR and 95% confidence intervals for each explanatory factor that was significant in the modeling are listed in Table 4. An OR of <1.0 means that the odds are decreased for that puppy condition to occur when the factor is present, compared with a litter in which the factor is not present. Conversely, when the OR is >1.0, the odds are increased for that puppy condition to occur when that factor is present, compared with a litter in which that factor is not present.

Modeling Evaluation

Model deviances relative to the model degrees of freedom all suggested adequate goodness of fit.

Post Hoc Analysis

In an effort to determine a reason for teaching institutions having a lower likelihood of all puppies spontaneously breathing compared to other practices [Table 4], post hoc testing was done. Factors tested were number of freshly dead, decomposed, or deformed puppies; percentage of cesarean-delivered puppies born alive; emergency surgery; and time from induction to delivery. These factors were selected based on the assumption that they might provide evidence of a difference in the patient population (e.g., emergency, decomposed puppies) or a specific difference in surgical management (e.g., time from induction to delivery) at teaching institutions. Teaching institutions had more emergency surgeries than predicted and had twice as long of a time from induction to delivery (median, 20 minutes; range, 2 to 50 minutes) compared to nonteaching institutions (median, 10 minutes; range, 9 to 55 minutes).

Vigor Factors

The three vigor characteristics—breathing, moving, and vocalizing—were clearly interrelated. The odds of having litters in which puppies were either moving or vocalizing were greater if all puppies were also breathing and either vocalizing or moving, respectively. This supports the common-sense view that puppies are generally breathing before they vocalize or move and that puppies that are active at birth are the healthiest, most robust, and most likely to survive the neonatal period. It also makes sense that breathing is the most critical parameter to examine.

Anesthetic Factors

A number of anesthetic drugs administered to the mother were associated with puppy vigor. The use of inhaled anesthetics decreased the odds that the litter would have all puppies breathing or any of the puppies moving at birth. Inhaled anesthetics depress ventilation. However, because isoflurane (0.2%) and halothane (25%) are minimally metabolized,⁶ ventilation is the primary route of drug elimination. Thus, neonatal respiratory depression cannot be reversed until the puppy breathes. This data confirms that it is important to maintain as light an anesthetic plane as possible when using any of the inhalant anesthetics in order to prevent self-perpetuating apnea. If the puppies are deeply anesthetized with inhalant anesthetics at the time of delivery and breathing is depressed, then other factors (e.g., tactile stimulation, environmental temperature, hypercapnia) might play a more important role in the puppy’s initial attempts to ventilate. In such situations, additional intervention such as intubating and artificially ventilating the newborn may be required to dissipate the anesthetic. Once the puppy starts to breathe, the inhalant anesthetic is eliminated rapidly. A delay in inhalant drug elimination might also account for the lower odds of puppies spontaneously moving in litters exposed to inhalant anesthetics. Similarly, there is evidence that human infants have a lower (i.e., worse) Apgar score following delivery under general anesthesia than following delivery with a local anesthetic technique.⁷ (An “Apgar” score measures the vigor of newborn human infants.⁸) It is unclear as to why only isoflurane, and not inhalants in general, was positively associated with litters having any puppies spontaneously vocalizing at birth but not positively associated with either breathing or moving.

Of all the injectable anesthetics that were tested [Table 3], only ketamine decreased the odds that the litter would have all puppies spontaneously breathing at birth. Ketamine has known depressant effects on cesarean-delivered puppies,⁹ primates,¹⁰ and children.¹¹

The only other injectable anesthetics associated with puppy vigor were the thiobarbiturates. Thiopental or thiamylal was associated with litters not having any puppies spontaneously moving at birth. This finding is counter to that in human medicine, in which barbiturates did not affect the initial Apgar score of infants.^12–14 The reason for this difference between puppies and human newborns cannot be determined from this study, although it might be due to differences in doses administered, pharmacodynamic species differences, or an interaction of a number of perioperative factors. For instance, when thiobarbiturates are used, the Apgar score is lower in human infants if they are delivered in <5 minutes after induction of anesthesia than if delivery is delayed,¹⁵ presumably because there is still a high blood concentration of the barbiturate in the newborn’s blood. In veterinary medicine, delivery time did not appear to influence puppy vigor, and dams induced with barbiturates did not have shorter or longer induction to delivery times than other dams (P=0.25; post hoc testing using Wilcoxon’s rank-sum test). Alternatively, thiobarbiturates may simply slow the locomotor activity in these puppies without affecting vital behavior such as breathing.

While the use of inhalant anesthetics, ketamine, and thiobarbiturates influenced puppy vigor, they do not influence neonatal mortality.¹ An earlier study indicated that the only anesthetics likely to increase puppy mortality were xylazine and methoxyflurane.¹ Therefore, using anesthetics that decrease puppy vigor characteristics might not necessarily directly compromise puppy survival. Although one should not necessarily avoid administering anesthetics that decrease puppy vigor if there are other medical indications for their use (e.g., cardiovascular stability to the dam), one should be aware that such puppies might require more intensive care to survive than litters in which those drugs were not used. Isoflurane was positively associated with only one of the vigor characteristics (i.e., vocalizing), but because increasing vigor is associated with greater puppy survival, this suggests that isoflurane is the preferred inhalant anesthetic to use for cesarean section.

Nonanesthetic Factors

Having surgery at a particular large private practice or having surgery at a private practice rather than a teaching institute were factors associated with the litter having all puppies breathing at birth. One particular private practice appears to have minimized those risk factors that adversely affect neonatal respiration, indicating that improvements in patient care are feasible and can affect puppy vigor. The increased risk of having some puppies born apneic at a teaching institute might be because such institutions receive a greater percentage of “at risk” patients. Post hoc results indicated more emergencies and twice as long times from induction to delivery. However, both of these factors were tested in the model [Table 1], and neither factor, by itself, influenced puppy vigor. The model looks at each factor independently of the other factors but does not evaluate for an interaction between factors (e.g., the effect of longer induction to delivery time on emergency cases). Hence, the authors cannot exclude the possibility of factor interactions or some other cause, such as longer driving time between initiation of labor and admission to the teaching hospital, to explain these results.

If the dam was not brachycephalic or if the dam was a Labrador retriever, these were factors associated with the litter having all puppies spontaneously vocalizing at birth. Puppies of brachycephalic breeds also have a higher mortality,¹ indicating that one should focus on these breeds as high-risk cases and that vigilant monitoring of puppies is required.

Study Limitations

The limitations imposed by the study design have been previously addressed.¹ The study’s primary limitation is that these results are specific to this population of dogs taken from this population of veterinary hospitals. However, the study sample was pooled, and the authors believe it to be sufficiently representative to permit general extrapolation of these findings to cesarean sections performed in the United States and Canada.