Death of a neonate born to a critically ill mother with COVID-19: a case report

Recently, we showed that both acute metabolic acidosis and respiratory acidosis stimulate parathyroid hormone (PTH) secretion in the dog. To evaluate the specific effect of acidosis, ionized calcium (iCa) was clamped at a normal value. Because iCa values normally increase during acute acidosis, we now have studied the PTH response to acute metabolic and respiratory acidosis in dogs in which the iCa concentration was allowed to increase (nonclamped) compared with dogs with a normal iCa concentration (clamped). Five groups of dogs were studied: control, metabolic (clamped and nonclamped), and respiratory (clamped and nonclamped) acidosis. Metabolic (HCl infusion) and respiratory (hypoventilation) acidosis was progressively induced during 60 min. In the two clamped groups, iCa was maintained at a normal value with an EDTA infusion. Both metabolic and respiratory acidosis increased (P < 0.05) iCa values in nonclamped groups. In metabolic acidosis, the increase in iCa was progressive and greater (P < 0.05) than in respiratory acidosis, in which iCa increased by 0.04 mM and then remained constant despite further pH reductions. The increase in PTH values was greater (P < 0.05) in clamped than in nonclamped groups (metabolic and respiratory acidosis). In the nonclamped metabolic acidosis group, PTH values first increased and then decreased from peak values when iCa increased by > 0.1 mM. In the nonclamped respiratory acidosis group, PTH values exceeded (P < 0.05) baseline values only after iCa values stopped increasing at a pH of 7.30. For the same increase in iCa in the nonclamped groups, PTH values increased more in metabolic acidosis. In conclusion, 1) both metabolic acidosis and respiratory acidosis stimulate PTH secretion; 2) the physiological increase in the iCa concentration during the induction of metabolic and respiratory acidosis reduces the magnitude of the PTH increase; 3) in metabolic acidosis, the increase in the iCa concentration can be of sufficient magnitude to reverse the increase in PTH values; and 4) for the same degree of acidosis-induced hypercalcemia, the increase in PTH values is greater in metabolic than in respiratory acidosis.

We report a case of asymptomatic COVID-19 infection in a pregnant woman in the third trimester with good maternal and infant outcomes. The patient was admitted to the Second People's Hospital of Hefei on February 11, 2020, because of a novel coronavirus nucleic acid test result for one at 38 weeks of gestation. No abnormality was observed during her previous regular prenatal examinations. A throat swab sample was obtained from the patient four days before admission due to the diagnosis of COVID-19 infection in her husband and sister on the 14th and 7th day before her admission, and the new coronavirus nucleic acid test showed positive. The patient reported no discomfort before admission. Chest CT on the 3rd after admission showed a small amount of bilateral pleural effusion. Irregular contractions occurred three days after admission and labor was considered to be imminent. An emergency cesarean section was performed and the patient delivered a live baby girl. No tests were performed on amniotic fluid, cord blood or placenta for new coronavirus nuclei acid. The patient was isolated from the infant without breastfeeding after surgery. All medical staff involved in the cesarean section were isolated after surgery. Neonatal peripheral blood and nasopharyngeal swabs were collected for the new coronavirus nucleic acid tests on the day of birth and one day of age respectively, and nasopharyngeal swabs and anal suabs were taken at nine days after birth. All test results were negative. The patient recovered well after surgery with stable vital signs. Chest CT on the 8th after operation showed a small amount of bilateral pleural effusion, while the new coronavirus nucleic acid test results of the pharyngeal swabs were positive on the 11th and 12th day after operation. The throat swabs of all medical staff involved in the operation were negative 14 days after the operation. The mother and baby were discharged 14 days after the Cesarean section.

The effects of acute respiratory versus metabolic acidosis on the myocardium and their consequences on adrenoceptor stimulation remain poorly described. We compared the effects of metabolic and respiratory acidosis on inotropy and lusitropy in rat myocardium and their effects on the responses to α- and β-adrenoceptor stimulations. The effects of acute respiratory and metabolic acidosis (pH 7.10) and their interactions with α and β-adrenoceptor stimulations were studied in isolated rat left ventricular papillary muscle (n=8 per group). Intracellular pH was measured using confocal microscopy and a pH-sensitive fluorophore in isolated rat cardiomyocytes. Data are mean percentages of baseline±SD. Respiratory acidosis induced more pronounced negative inotropic effects than metabolic acidosis did both in isotonic (45±3 versus 63±6%, P<0.001) and isometric (44±5 versus 64±3%, P<0.001) conditions concomitant with a greater decrease in intracellular pH (6.85±0.07 versus 7.12±0.07, P<0.001). The response to α-adrenergic stimulation was not modified by respiratory or metabolic acidosis. The inotropic response to β-adrenergic stimulation was impaired only in metabolic acidosis (137±12 versus 200±33%, P<0.001), but this effect was not observed with administration of forskolin or dibutiryl-cyclic adenosine monophosphate. This effect might be explained by a change in transmembrane pH gradient only observed with metabolic acidosis. The lusitropic response to β-adrenergic stimulation was not modified by respiratory or metabolic acidosis. Acute metabolic and respiratory acidosis induce different myocardial effects related to different decreases in intracellular pH. Only metabolic acidosis impairs the positive inotropic effect of β-adrenergic stimulation.

Clinically, a decrease in blood pH may be due to either a reduction in bicarbonate concentration ([HCO(-)(3)], metabolic acidosis) or an increase in PCO(2) (respiratory acidosis). In mammals, metabolic acidosis induces a far greater increase in urine calcium excretion than respiratory acidosis. In cultured bone, metabolic acidosis induces a marked increase in calcium efflux and a decrease in osteoblastic collagen synthesis, whereas isohydric respiratory acidosis has little effect on either parameter. We have shown that metabolic acidosis prevents the normal developmental increase in the expression of RNA for matrix Gla protein and osteopontin in chronic cultures of primary murine calvarial bone cells (predominantly osteoblasts) but does not alter expression of osteonectin. To compare the effects of isohydric metabolic and respiratory acidosis on expression of these genes, bone cell cultures were incubated in medium at pH approximately 7.2 to model metabolic ([HCO(-)(3)], approximately 13 mM) or respiratory (PCO(2), approximately 80 mmHg) acidosis or at pH approximately 7.4 as a control. Cells were sampled at weeks 4, 5, and 6 to assess specific RNA content. At all time periods studied, both metabolic and respiratory acidosis inhibited the expression of RNA for matrix Gla protein and osteopontin to a similar extent, whereas there was no change in osteonectin expression. In contrast to the significant difference in the effects of metabolic and respiratory acidosis on bone calcium efflux and osteoblastic collagen synthesis, these two forms of acidosis have a similar effect on osteoblastic RNA expression of both matrix Gla protein and osteopontin. Thus, although several aspects of bone cell function are dependent on the type of acidosis, expression of these two matrix genes appears to be regulated by extracellular pH, independently of the type of acidosis.

To the Editor: To date, coronavirus disease 2019 (COVID-19) has spread all over the world. As the exact sources of the virus, the time of virus shedding after infection and viral propagation are still undefined, there are still great challenges in controlling the virus spreading and the treatment of infection. Rapid diagnosis of infection cases and early isolation are extremely important for the overall prevention and control work.[1] Therefore, rapid diagnosis of infection cases and early isolation are extremely important for overall disease prevention and control.[2] In recent days, network media reported confirmed COVID-19 cases with more than two negative nucleic acid testing results at an early stage. However, detailed reports are still lacking. Therefore, we report here the history and clinical data of a confirmed case with negative 2019 novel coronavirus (2019-nCoV) nucleic acid test results within 8 days of onset and the final positive test result confirmed on the 11th day of onset in the Shenzhen University General Hospital. A 47-year-old woman who traveled to Wuhan on January 13, 2020 with her mother (who was later confirmed to be infected with the COVID-19) had an intermittent fever (highest body temperature: 37.9°C) on January 20, 2020 accompanied by coughing. Two days later, she was admitted to the Third People's Hospital of Shenzhen. Initially, her blood test revealed a normal white blood cell count (4.94 × 109/L) and decreased lymphocyte count (1.06 × 109/L), with an oxygen saturation level of 99%. After admission, the patient received atomized inhalation of interferon twice daily. 2019-nCoV nucleic acid testing by sampling from a throat swab on January 22 and 28 failed to show positive results. On June 29, 2020, the patient was transferred to the Shenzhen University General Hospital for further isolation and clinical observation. At admission (day 9 of onset), the patient had worsened headache and cough, but her body temperature (36.0–37.2°C) and oxygen saturation level (99%) remained relatively normal. Her blood test result showed a normal white blood cell count (5.81 × 109/L) and decreased lymphocyte count (0.91 × 109/L). Chest computed tomography revealed bilateral ground-glass opacity [Figure 1]. Besides atomized inhalation of interferon, oseltamivir (75 mg) was orally administered twice daily.Figure 1: Continuous chest computed tomography scans of the patient. (A) shows multiple ground-glass density shadows in the lower lobe of both lungs at the level of the aortic arch (B–D) are continuous faults extending downward.On January 31 (day 11 of onset), the blood gas analysis of the patient revealed dramatic deterioration (partial pressure of oxygen, 65.5 mmHg; partial pressure of carbon dioxide, 39.2 mmHg; and sulfur dioxide, 93.6%). 2019-nCOV nucleic acid testing was performed again by sampling from nasal swabs. The result showed positivity for COVID-19 infection, which was also verified by the Centers for Disease Control. According to the New Coronavirus Infection Pneumonia Protocol (version 6) published by the National Health Commission of the People's Republic of China, two consecutive negative respiratory 2019-nCoV nucleic acid test results (at least 1 day apart) are required for exclusion of COVID-19.[3] However, cases with highly suspected epidemiological history, typical clinical, laboratory, and radiological characteristics cannot be excluded. In the present case, the patient had a definite epidemiological history, characteristic pulmonary imaging findings, and typical clinical symptoms. However, no virus nucleic acid sequence was detected for 8 days and until the 11th day of onset, indicating the presence of a non-parallel relationship between 2019-nCoV nucleic acid testing and clinical symptoms. At present, nasal and throat swabs are often used for sampling of specimens for 2019-nCoV nucleic acid testing. The previous research conducted on influenza virus diagnostic tests showed that influenza viruses of different sub-types preferentially localized at different sites, resulting in a variation in the positive detection rates from different sampling sites.[3] To date, the exact biological characteristics of COVID-19 are still undefined, including its variant sub-types or preferred localizing sites.[4] Therefore, for this case, we suspect that changing the sampling site from the throat to the nasal region might have contributed to the positive result. At the time of write this case report, we had four patients with negative throat swabs who later tested positive using nasal swabs. The digestive system is another route for 2019-nCoV infection,[5] also suggesting that the localizing sites of the 2019-nCoV may differ based on route of infection. Accordingly, for patients with suspicion of COVID-19, multiple site sampling is conducive to earlier detection of 2019-nCoV. In addition, the status of the patients shortly before sampling should also be taken into consideration, as anti-viral nebulization treatment might influence the positive detection rate. Efforts need to be made to improve the efficiency of virus detection at an early stage for better prevention and control of the spread of the COVID-19. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. The patient has given her consent for the publication of her images and other clinical information in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed. Funding This study was supported by a grant from the Sanming Project of Medicine in Shenzhen (No. SZSM201911007). Conflicts of interest None.

The complications of cesarean section are seen more commonly in emergency than in elective cases. The aim of this study was to find out the incidence of cesarean section in Nepal Medical College Teaching Hospital and to compare the maternal and fetal outcome in elective and emergency cesarean section. A prospective study of all the cases undergoing cesarean section in Nepal Medical College Teaching Hospital was carried out during the period of six months from Asar 2069 to Mangsir 2069. The incidence of cesarean section was 254 (22.30%) out of which emergency cesarean section accounted for 167 (65.7%) and elective cesarean section for 87 (34.3%). The usual indications of emergency cesarean section were fetal distress, previous cesarean section in labour, non progress of labour and prolonged second stage of labour. The usual indications of elective cesarean section were previous cesarean section, breech, cephalopelvic disproportion and cesarean section on demand. There was found to be no significant difference in age, period of gestation, blood loss and blood transfusion in emergency vs. elective cesarean section. There was significant difference seen in the length of hospital stay, fever, urinary tract infection, wound infection and low APGAR in five minutes indicating that these were more common in emergency cesarean section. Significant difference was also seen in the incidence of postpartum haemorrhage indicating that it was seen more in elective cesarean section. The incidence of cesarean section in Nepal Medical College Teaching Hospital is high and the overall complication rate is higher in emergency cesarean section than in elective cesarean section.

1. Effective renal plasma flow, glomerular filtration rate and cardiac output were measured in osmotically loaded dogs before and during comparable acute respiratory and metabolic acidosis. 2. Urine output increased in control dogs and in animals with metabolic acidosis, but declined with respiratory acidosis. Effective renal plasma flow and glomerular filtration rate declined with respiratory and metabolic acidosis. 3. When respiratory acidosis was buffered with sodium bicarbonate, urine volume increased and glomerular filtration rate and effective renal plasma flow were unchanged; with trihydroxymethylaminomethane, urine volume increased but glomerular filtration rate and effective renal plasma flow fell. 4. When metabolic acidosis was buffered with sodium bicarbonate, urine volume increased; with trihydroxymethylaminomethane, urine volume increased but glomerular filtration rate fell. Cardiac output declined only during metabolic acidosis, both buffered and unbuffered. 5. These studies demonstrate that, even with osmotic loading: (1) respiratory acidosis caused a decrease in glomerular filtration rate, effective renal plasma flow and urine volume; (2) metabolic acidosis depresses glomerular filtration rate and effective renal plasma flow but does not change urine volume even though cardiac output falls; (3) sodium bicarbonate is mor effective than trihydroxymethylaminomethane in preserving renal function during respiratory and metabolic acidosis.

The mammalian proximal tubule is an important mediator of the renal adaptive response to systemic acidosis. In chronic metabolic and respiratory acidosis the bicarbonate reabsorptive (or proton secretory) capacity is increased. This increase is mediated, at least in part, by an increase in Vmax of the luminal Na/H antiporter. To determine whether this adaptation involves increased mRNA expression, Na/H antiporter mRNA levels were measured by Northern analysis in renal cortex of rats with metabolic (6 mmol/kg body wt NH4Cl for 2 or 5 d) and respiratory (10% CO2/air balanced for 2 or 5 d) acidosis and of normal, pair-fed rats. Na/H antiporter mRNA levels were unchanged after 2 d of both metabolic and respiratory acidosis. After 5 d, however, Na/H antiporter mRNA expression was increased 1.76 +/- 0.12-fold in response to metabolic acidosis (P less than 0.005, n = 8), but was not different from normal in response to respiratory acidosis: 1.1 +/- 0.2 (NS, n = 8). Thus, the renal adaptive response to metabolic acidosis involves increased cortical Na/H antiporter mRNA levels. In contrast, the enhanced proximal tubule Na/H antiporter activity and bicarbonate reabsorption in respiratory acidosis seem to involve mechanisms other than increased Na/H antiporter gene expression.

Background To determine the changes in emergency and elective caesarean section (CS) rates since the COVID-19 pandemic, identify the groups most affected, and examine changes in the factors associated with CS rates, and reasons for CS. Methods We conducted a retrospective cohort study using routinely collected data of 22,346 births from before the pandemic (January 2018–February 2020) and 18,597 births during the pandemic (March 2020–December 2021). Data were analysed using multinominal logistic regression. Results The CS rate increased by 4.1% (from 30.1% to 34.2%), reflecting increases of 2.3% in emergency CS (from 11.5% to 13.8%) and 1.7% in elective CS (from 18.7% to 20.4%). Large groups with notable increases were women who were nulliparous (7.2% increase), from South Asia (6.0%), obese (5.2%) and giving birth at a small hospital (6.1%). Compared to pre-pandemic, the relative risk of an emergency CS versus a vaginal delivery increased 1.36 times (adjusted relative risk ratio (aRRR) = 1.36; 95% CI = 1.27, 1.45) and the risk of having an elective CS increased 1.11 times (aRRR = 1.11; 95% CI = 1.04, 1.20). Factors associated with both emergency and elective CS were age, region of birth, reproductive history, body mass index, hypertension, diabetes, mode of antenatal care and hospital. Socio-Economic Indexes for Areas and antenatal care were only associated with elective CS. Baby gender was only associated with emergency CS. Preterm gestation at delivery was associated with reduced emergency but increased elective CS. Foetal compromise was the most common indication for emergency CS (43.2%) and increased the most (8.0%). Previous CS was the most common indication for elective CS (61.5%) and reduced the most (1.9%). Conclusions Both emergency and elective CS rates increased significantly during the pandemic, with the former increasing at a higher rate. The persistent upward trend of CS rates, exacerbated by increasing proportions of nulliparous women undergoing CSs, is concerning.

<h3>Objective:</h3> With this study we aimed to assess the association of respiratory and metabolic acidosis in ICH with functional outcome and mortality. <h3>Background:</h3> Systemic Acidosis is common in critical care settings and patients with intracerebral hemorrhage (ICH) frequently require intubation and ICU admission. The association between ICH and systemic acidosis has not been investigated. <h3>Design/Methods:</h3> Retrospective single center cohort of patients with acute spontaneous ICH. We examined the relationship between acidosis on admission and (1) hospital mortality and (2) 90-day modified Rankin Scale (mRS) dichotomized as unfavorable (&gt;3) vs favorable (≤3). Metabolic acidosis was defined by the presence of one of the following: Serum bicarbonate &lt;22 mEq/L, lactic acid &gt;2 mmol/L or pH &lt;7.35. Respiratory acidosis was defined by pCO2 &gt;45 mmHg. We further stratified our analysis by ICU vs general ward admission and intubation status. <h3>Results:</h3> There was a total of 406 patients, average age 80.5 (±1.5) years, 174 (43%) females and 232 (57%) males. 134 (33%) patients were acidotic on admission, 42 (10%) had respiratory acidosis and the remaining 92 (23%) had metabolic acidosis. There was no statistically significant association between metabolic acidosis with either hospital mortality (p=0.21, 95% CI [0.37–1.24]) or 90-day favorable functional outcome (p=0.61, 95% CI [0.37–1.24]) after adjustment for hematoma volume and expansion, Glasgow Coma Scale, and presence of interventricular hemorrhage. There was no association between respiratory acidosis with either hospital mortality (p=1.00) or functional outcome (p=1.00) before the adjustment for confounders. There was no effect modification after stratifying by ICU and intubation status. <h3>Conclusions:</h3> In this retrospective cohort study, we found that systemic acidosis was present in one third of patients with spontaneous ICH. Unlike other critical neurological conditions such as traumatic brain injury, there was no significant association between metabolic and respiratory acidosis with mortality and 90-day functional outcome in ICH. <b>Disclosure:</b> Dr. Andreev has nothing to disclose. Dr. Wilson has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Forsman has stock in Eli Lilly and Co. Dr. Forsman has stock in Moderna Inc. Dr. McMillan has nothing to disclose. Dr. Sahni has nothing to disclose. Dr. Selim has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MedRhythms Inc.. Dr. Lioutas has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Qmetis. Dr. Lioutas has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Heart Association.

Acute kidney injury (AKI) is a common complication in hospitalized patients, with an incidence of 3 to 10% (1–4). In-hospital mortality rates that are associated with AKI remain high, in the range of 30 to 70% (5–8), despite significant improvements in dialytic technology as well as important advances in critical care, which have resulted in improved survival for other critical illnesses, including acute lung injury and sepsis (9). These improvements include continuous renal replacement therapies, which allow for continuous removal of solutes and fluid and may be tolerated better from a hemodynamic standpoint, and biocompatible dialysis membranes, which are associated with reduced complement and granulocyte activation. In general, indications for dialysis in the acute care setting have been extrapolated from those that are applied in chronic kidney disease, including volume overload that is refractory to diuretic therapy; electrolyte abnormalities (in particular hyperkalemia); uremic complications (pericarditis or pleuritis); severe acidosis (pH < 7.20); and selected toxic ingestions, such as methanol, ethylene glycol, and other water-soluble agents (10,11). However, the evidence base supporting specific dialysis practices in the acute care setting is limited. For example, several studies that were completed in the 1960s and 1970s compared “early” and “late” initiation of dialysis, using blood urea nitrogen (BUN) to define early and late (Table 1). These studies primarily were cohort studies that used historical controls, not randomized, clinical trials. The results of these investigations, along with extrapolation from the ESRD population, promoted recent practice patterns. Currently, many nephrologists often delay dialysis in the acute care setting until the patient has an impending complication of AKI, such as hyperkalemia leading to cardiac arrhythmias, acidosis resulting in hypotension, or oliguria leading to volume overload or hypoxemia, or until the BUN exceeds 100 mg/dl (18). Given differences in protein catabolism, …

Objective: This study has aimed to share the perioperative management practices and respective outcomes in patients; who underwent urgent thoracotomy due to traumatic hemothorax during the pandemic.Methods: In a single-center, 18 patients; who underwent urgent thoracotomy due to traumatic hemothorax in March 2020 to March 2021, were included in the study retrospectively. Patient data were retrieved from digital archive files. The initial evaluation was performed in the emergency room while wearing complete personal protective equipment. Patients were taken into the operating room under emergency conditions without waiting for the results of the nucleic acid tests performed on oropharyngeal and nasopharyngeal swabs. The operation was carried out by involving the minimum number of personnel. In the postoperative period, patients were followed up in a negative pressure intensive care room. Isolation measures were maintained until two novel coronavirus nucleic acid tests on oropharyngeal and nasopharyngeal swabs collected 48 hours apart were reported as negative.Results: During the one-year period in the COVID-19 pandemic, 18 patients were operated on with the indication of urgent thoracotomy. Of the patients, 14 were men (77.8%), and 4 were women (22.2%). Nucleic acid test results were negative in 17 patients (94.5%). The nucleic acid test result was reported positive in one patient (5.5%) for samples taken at the 48th hour. Nucleic acid tests were performed on the oropharyngeal and nasopharyngeal swabs obtained on the fifth and seventh days from the operation personnel. No novel coronavirus transmission occurred in the healthcare personnel. In the postoperative period, 15 patients (83.3%) were successfully treated and discharged from the hospital, but 3 patients (16.7%) died. No morbidity or mortality occurred due to COVID-19.Conclusion: Urgent thoracotomies can be successfully performed during the COVID-19 pandemic. Novel coronavirus transmissions can be avoided if relevant healthcare personel comply with isolation measures and use complete personnel protective equipment

The effects of a metabolic and respiratory acidosis and alkalosis on intracellular pH (pHi) and K+ have been compared in cardiac and skeletal muscle from the anesthetized rabbit. The extracellular space and pHi were calculated from the distribution volumes of [51Cr] EDTA and [14C]DMO, respectively. When pHe was varied by altering PCO2, the slope of the line relating pHi to the extracellular pH (pHe) was greater (P less than 0.05--0.001) than that obtained during metabolic changes of pHe in right and left ventricles, atria, diaphragm, and quadriceps. During metabolic acidosis and alkalosis, the slope of pHi/pHe line did not vary between tissues. During respiratory acidosis, there was no difference in slope between cardiac tissues, but it was less in left ventricle than quadriceps (P less than 0.001). In left ventricle intracellular K+ increased in a metabolic (P less than 0.05) or respiratory acidosis (P less than 0.02), whereas in diaphragm it decreased (P less than 0.02). Intracellular K+ correlated with pHe and pHE-PHi. Changes in pHi but not intracellular K+ could explain known differences in myocardial function in respiratory and metabolic acidosis.

The acidosis of pulmonary edema

Two respiratory-related areas, the para-facial respiratory group/retrotrapezoid nucleus (pFRG/RTN) and the pre-Bötzinger complex/ventral respiratory group (preBötC/VRG), are thought to play key roles in respiratory rhythm. Because respiratory output patterns in response to respiratory and metabolic acidosis differ, we hypothesized that the responses of the medullary respiratory neuronal network to respiratory and metabolic acidosis are different. To test these hypotheses, we analysed respiratory-related activity in the pFRG/RTN and preBötC/VRG of the neonatal rat brainstem-spinal cord in vitro by optical imaging using a voltage-sensitive dye, and compared the effects of respiratory and metabolic acidosis on these two populations. We found that the spatiotemporal responses of respiratory-related regional activities to respiratory and metabolic acidosis are fundamentally different, although both acidosis similarly augmented respiratory output by increasing respiratory frequency. PreBötC/VRG activity, which is mainly inspiratory, was augmented by respiratory acidosis. Respiratory-modulated pixels increased in the preBötC/VRG area in response to respiratory acidosis. Metabolic acidosis shifted the respiratory phase in the pFRG/RTN; the pre-inspiratory dominant pattern shifted to inspiratory dominant. The responses of the pFRG/RTN activity to respiratory and metabolic acidosis are complex, and involve either augmentation or reduction in the size of respiratory-related areas. Furthermore, the activation pattern in the pFRG/RTN switched bi-directionally between pre-inspiratory/inspiratory and post-inspiratory. Electrophysiological study supported the results of our optical imaging study. We conclude that respiratory and metabolic acidosis differentially affect activities of the pFRG/RTN and preBötC/VRG, inducing switching and shifts of the respiratory phase. We suggest that they differently influence the coupling states between the pFRG/RTN and preBötC/VRG.