Delayed Onset Hypercapnia in Patients With Anemia Undergoing Total Laparoscopic Hysterectomy: A Report of 2 Cases

Introduction

Hypercapnia is defined as the elevation of partial pressure of arterial CO2 (PaCO2) above 45 mmHg, typically resulting from either increased CO2 production metabolically or respiratory failure [1]. Clinical presentation can vary depending on the source of the hypercapnia, with the typical presentation including altered consciousness, respiratory acidosis, tachycardia, hypertension, and, in severe cases, seizures or syncope [1]. Diagnosis is established primarily by arterial blood gas analysis (ABG) demonstrating elevated PaCO2 with corresponding acid-base changes, while ancillary investigations are used to identify the underlying cause and contributing factors. The management focuses on identifying the underlying cause, optimizing ventilation, and providing ventilatory support when indicated [1].

Laparoscopic surgery is now routinely used due to its numerous benefits, including less discomfort after surgery, faster healing, and shorter hospital stays, compared with open surgeries [2,3]. The formation of a pneumoperitoneum, typically with CO2, is a crucial aspect of laparoscopy due to its high blood solubility and low combustibility. This can reduce the risk of gas embolism and facilitates rapid gas elimination [3]. Nevertheless, the systemic absorption of insufflated CO2 during pneumoperitoneum, reduced lung compliance, ventilatory-perfusion mismatch, and patient positioning can contribute to intraoperative and early postoperative hypercapnia [3–5]. Although intraoperative ventilatory adjustments usually normalize CO2 levels, absorption of CO2 can continue after desufflation, leaving some patients susceptible to delayed postoperative hypercapnia [4].

The physiological effects of absorption of CO2 during pneumoperitoneum include respiratory and cardiovascular alterations. Hypercarbia developing minutes after CO2 insufflation can lead to myocardial depression, arrhythmias, systemic vasodilation, and an aggravation of pulmonary hypertension [4,6]. Even after desufflation, a period of increased ventilation is often required to eliminate remaining CO2 and stabilize arterial CO2 levels [4]. The steep Trendelenburg position commonly used during laparoscopic hysterectomy further complicates ventilation by reducing lung compliance and functional residual capacity, promoting ventilation–perfusion mismatch and CO2 retention [5,7]. While most healthy persons tolerate these physiological alterations with appropriate intraoperative treatment, patients with comorbidities such as anemia can be at risk of protracted or delayed hypercapnia [8–10].

Hemoglobin plays a critical role in CO2 carriage via carbaminohemoglobin formation and acid-base buffering [10]. Anemia may impair CO2 transport and buffering due to decreased hemoglobin availability, limiting the body’s ability to compensate for acute CO2 loads [8–11]. Experimental and physiological studies demonstrate that reduced buffer power amplifies respiratory acidosis during hypercapnic states, even when ventilation appears adequate [8,11]. This mechanism may be particularly relevant during laparoscopic surgery, when CO2 load is increased, suggesting that severe anemia may increase the risk of postoperative respiratory acidosis [8,9].

Past accounts of post-laparoscopic delayed-onset hypercapnia are often linked to subcutaneous emphysema, in which CO2 retained in soft tissues is gradually absorbed after surgery, leading to respiratory acidosis after extubation [12]. In contrast, neither of our patients had clinical or radiological evidence of subcutaneous emphysema or intraoperative complications that could explain the postoperative respiratory acidosis and hypercapnia. These observations prompted us to explore alternative mechanisms.

Anemia is known to increase postoperative morbidity following laparoscopic hysterectomy. Tyan et al in a large cohort study reported that increased severity of anemia was independently associated with higher postoperative complication rates in patients undergoing laparoscopic hysterectomy for benign indications [13]. However, delayed-onset postoperative hypercapnia was not specifically described, and the underlying mechanisms were not explained.

Taken together, these 2 cases describe delayed-onset hypercapnia and respiratory depression in severely anemic patients following laparoscopic hysterectomy with CO2 pneumoperitoneum. Both cases occurred in the absence of subcutaneous emphysema or apparent intraoperative complications. These observations highlight a potential but underrecognized risk in anemic patients and emphasize the importance of enhanced postoperative monitoring and individualized ventilatory strategies in high-risk patients.

Case Reports

CASE 1:

A 43-year-old woman with American Society of Anesthesiologists (ASA) physical status I presented with a history of heavy menstrual bleeding for 1 year, which was unresponsive to medical management. She was scheduled for laparoscopic hysterectomy. Her preoperative assessment revealed no respiratory, cardiovascular, or neurological comorbidities. Pulmonary auscultation and chest radiography were normal. She was a non-smoker. Her preoperative hemoglobin level was 7.3 g/dL despite iron treatment. She declined intravenous (IV) iron therapy, and the surgery was scheduled with intraoperative transfusion of 1 unit of blood at the beginning of surgery.

Routine induction was performed with propofol, morphine, and rocuronium. The patient was placed in the Trendelenburg position. Capnoperitoneum was established and maintained for 45 minutes. The surgery was uncomplicated, with an estimated blood loss of 50 mL. At the end of 55 minutes, breathing attempts were noted, and residual effects of rocuronium was reversed with IV neostigmine 2.5 mg and IV atropine 1.2 mg. The patient was placed in the supine position. Capnography at this point revealed an end-tidal CO₂ (EtCO₂) level of 75 mmHg. She was hyperventilated for 10 minutes before being allowed spontaneous breathing, followed by a fully awake extubation. At this point, vital signs were stable, and the patient showed no clinical signs of inadequate neuromuscular reversal.

Fifteen minutes after extubation, the patient became unresponsive. However, she remained hemodynamically stable, with shallow breathing. Differential diagnoses included subcutaneous emphysema, opioid overdose, residual neuromuscular blockade, hypoglycemia, and hypercapnic encephalopathy. There were no signs of subcutaneous emphysema on physical examination and chest radiography. Her blood sugar level was normal. The absence of pinpoint pupils or bradycardia made opioid toxicity unlikely. A nerve stimulator was used at this point to check for the effect of residual neuromuscular blockade. All 4 twitches were present in train-of-four (TOF), indicating no residual muscle paralysis. ABG analysis showed respiratory acidosis, with a PaCO₂ of 88 mmHg and pH 7.01 (Table 1). The patient was reintubated and ventilated for 2 hours. This decision was made on the basis of persistent hypercapnia, with decreased consciousness suggesting hypercapnic encephalopathy. Extubation was performed after confirming normal acid-base balance, and the patient had an uneventful recovery.

CASE 2:

A 45-year-old woman with ASA I presented with heavy menstrual bleeding that was unresponsive to oral and IV iron therapy. She was scheduled for total laparoscopic hysterectomy. Preoperative assessment of cardiovascular and respiratory systems revealed no comorbidities. Her preoperative hemoglobin level was 8.1 g/dL.

Routine general anesthesia was administered with IV propofol, morphine, and rocuronium, and 1 unit of blood was transfused at induction. Capnoperitoneum was maintained for 65 minutes. The procedure was surgically challenging due to the presence of a large fibroid, necessitating prolonged dissection. The estimated blood loss was 75 mL. Toward the end of the procedure, EtCO₂ levels exceeded 75 mmHg, prompting hyperventilation for 10 minutes. The patient was then allowed to breathe spontaneously, and with the detection of spontaneous breathing attempts, IV neostigmine 2.5 mg with IV atropine 1.2 mg was given. She was extubated fully awake with good respiratory and hemodynamic parameters.

However, 10 minutes after extubation, she became unresponsive, with hypertension, a heart rate of 112 bpm, a bounding pulse, and dilated pupils. Differential diagnoses included intracranial event, inadequate reversal, opioid effects, or hypercapnia. No signs of opioid overdose or subcutaneous emphysema in physical examination and chest radiography were noted. A nerve stimulator was used in the upper limb, showing all 4 twitches in TOF, excluding the possibility of inadequate reversal of neuromuscular blockage. ABG analysis revealed respiratory acidosis, with a PaCO2 of 88 mmHg and pH 7.06 (Table 1). The patient was manually ventilated with the use of a bag valve mask for 5 minutes, after which she regained consciousness and made an uneventful recovery. Noninvasive support was prepared but not required. The transient nature of the episode and rapid recovery suggested delayed CO2 clearance as the underlying cause.

Discussion

These cases demonstrate that severe anemia can predispose patients undergoing laparoscopic hysterectomy to delayed onset postoperative hypercapnia despite apparently adequate intraoperative ventilation and full neuromuscular recovery. In both cases, marked respiratory acidosis with hypercapnia occurred after extubation, necessitating assisted ventilation, even though the intraoperative courses were uneventful and ventilatory management appeared appropriate. The key learning point from this report is that anesthesiologists and perioperative teams should be aware of the potential for delayed hypercapnia in anemic patients following CO2 pneumoperitoneum, even when standard intraoperative ventilatory strategies are applied [4,8,9,11].

In both cases, severe postoperative hypercapnia occurred in the presence of significant anemia, suggesting impaired CO2 transport and buffering as a contributing mechanism. Hemoglobin carries about 20% to 30% of CO2 as carbaminohemoglobin and plays a central role in acid-base buffering [9,10]. In severely anemic individuals, the reduced hemoglobin content significantly reduces this non-carbonic buffering capacity, limiting the effective sequestration and transfer of CO2 from the tissues to the lungs [8,11]. When ventilatory support is stopped after extubation, this can result in the accumulation and delayed release of CO2 from peripheral tissues into circulation, manifesting as delayed hypercapnia [4].

Despite sufficient intraoperative ventilation and normocapnic EtCO2 levels prior to extubation, both patients had markedly elevated PaCO2 levels of 88 mmHg postoperatively, suggesting a delayed CO2 shift from tissues rather than primary ventilatory failure. Temporary washout of CO2 during intraoperative hyperventilation can mask this phenomenon on capnography, further hiding the imminent danger [4]. This mechanism aligns with recent literature by Wagner, which discusses impaired CO2 carriage in altered physiological status [11].

Ventilation–perfusion mismatch and CO2 retention are well-recognized consequences of pneumoperitoneum, which raises intra-abdominal pressure, restricts diaphragmatic excursion, and lowers pulmonary compliance [4,5]. The steep Trendelenburg position intensifies these effects by encouraging cephalad displacement of the diaphragm and decreasing functional residual capacity [5,7]. Even after desufflation, ongoing absorption of CO2 from peritoneal surfaces enters the systemic circulation and this process can continue for a few hours after surgery [3,4]. This is usually offset by increased alveolar ventilation in healthy individuals. However, in the early postoperative period – when spontaneous breathing may be inadequate – this continuous CO2 load can cause acute respiratory acidosis in the context of anemia [4,8]. In our 2 patients, prolonged pneumoperitoneum combined with steep Trendelenburg positioning likely increased systemic CO2 load, which may have exceeded the reduced buffering capacity associated with anemia in the immediate postoperative period.

There have been prior reports of delayed hypercapnia in relation to subcutaneous emphysema, in which retained CO2 gradually returns to the systemic circulation after surgery [4,12]. However, neither of our patients demonstrated clinical signs such as palpable crepitus or radiological evidence of surgical emphysema, distinguishing these cases from previously reported mechanisms. This suggests an alternative pathophysiological mechanism, specifically decreased CO2 buffering brought on by anemia, expanding the differential diagnosis for delayed postoperative hypercapnia. Tyan et al discovered the association of postoperative morbidity following laparoscopic hysterectomy and reported that increasing anemia severity independently predicted postoperative complications. However, delayed onset hypercapnia was not specifically described, nor were physiological mechanisms explored [13]. Our cases extend these observations by proposing impaired CO2 clearance as a potential contributor to postoperative morbidity in patients with anemia.

In both of our patients, spontaneous ventilation in the immediate postoperative period was insufficient to compensate for ongoing CO2 absorption, despite full neuromuscular recovery and hemodynamic stability. The maintenance of normocapnia is largely dependent on alveolar ventilation. Following extubation, spontaneous breathing can be further impaired by sedation, muscle relaxation, diminished consciousness, and poor respiratory mechanics as a result of posture, particularly following lengthy surgery [4,5]. In both instances, we used intraoperative hyperventilation shortly after desufflation. However, CO2 levels rose again after extubation, most likely due to insufficient spontaneous breathing and continued systemic absorption. Extubation was performed only after full reversal of neuromuscular blockade, consistent with standard safety recommendations. Reintubation with mechanical ventilation (Case 1) and manual ventilation (Case 2) were chosen based on the clinical status of the patients. Noninvasive ventilation was considered but not used in view of rapid improvement or the need for more definitive airway support. The different management approaches in Case 1 and Case 2 reflect the spectrum of clinical severity observed in our patients, while supporting delayed CO2 clearance as the common underlying mechanism. Alternative ventilation strategies, such as staged weaning from mechanical ventilation, extended observation in a monitored setting, and delayed extubation in selected cases, have been discussed in lung-protective and individualized ventilation trials during laparoscopic surgery [7]. There is limited literature guiding this decision-making, particularly in anemic patients; our report adds to this evolving clinical understanding.

Conclusions

These cases demonstrate that delayed-onset postoperative hypercapnia can occur in severely anemic patients following total laparoscopic hysterectomy, even in the absence of subcutaneous emphysema or intraoperative complications. The combination of continued CO2 absorption from pneumoperitoneum and reduced hemoglobin-mediated buffering appears to impair postoperative CO2 clearance, leading to clinically significant respiratory acidosis.

Anemia should therefore be recognized as an important risk factor for delayed onset hypercapnia following laparoscopic surgery. Awareness of this association can aid early recognition and prompt ventilatory support in the postoperative period, improving patient safety in susceptible individuals.