Sickle Cell Disease

Many types of abnormal Hb are observed in sickle cell disease. However, only Hb SS (homozygous sickle cell Hb), Hb SC, and Hb S-β-thalassemia can cause severe clinical problems. Hypoxemia, acidosis, polycythemia, infection, and a high proportion of abnormal Hb concentration are the main risk factors for sickle cell disease complications. The following sickle cell crises can be life threatening: acute chest syndrome, stroke, acute splenic sequestration, aplastic crisis, and infection. General management always includes optimization of oxygenation, adequate analgesia, and treatment of the precipitating cause of the crisis.⁴ Hyperhydration is also recommended in most instances, but fluid requirements must be adapted with caution in patients with respiratory symptoms or pulmonary hypertension. Red blood cell (RBC) transfusion is a cornerstone of therapy, aiming to decrease abnormal Hb while maintaining hematocrit below 35%. An exchange transfusion should be considered in severe cases, especially in acute chest syndrome or stroke.

Acute chest syndrome is a leading cause of morbidity and mortality in sickle cell disease.^5,6 It is defined by the development of a new pulmonary alveolar infiltrate involving at least one complete lung segment, accompanied by fever, chest pain, tachypnea, cough, and hypoxia. Severe forms are analogous to acute respiratory distress syndrome. Acute chest syndrome results from intricate mechanisms including pulmonary infection (mostly by atypical bacteria and virus), fat embolization, and local vaso-occlusion.⁶ Perturbation of nitric oxide metabolism⁷ and hypercoagulability have also been demonstrated.⁶ Growing evidence suggests that pulmonary hypertension play a crucial role during sickle cell disease evolution, which may lead to abrupt severe right heart failure.⁶ Besides general management and empirical antibiotic therapy, covering atypical bacteria and Streptococcus pneumoniae, incentive spirometry is encouraged. Mechanical ventilation may be required to improve oxygenation; noninvasive ventilation can be successful.⁸ Owing to disturbance of nitric oxide metabolism, inhaled nitric oxide has been used in small trials or case reports, but its efficacy remains to be validated.⁹

Stroke must be considered in patients with sudden onset of neurologic symptoms. Specific management includes an urgent exchange transfusion and careful attention to neurologic worsening. Intracranial pressure monitoring can be helpful in severe stroke.

During acute splenic sequestration crisis, the blood volume retained in the spleen may lead to severe hypovolemic shock. An acute reduction of Hb concentration of 2 g/dL or more, with no other cause of blood loss, is considered diagnostic. Aplastic crisis can also cause an acute and severe anemia, usually during a viral infection, particularly with parvovirus B19. The half-life of RBCs is severely shortened in patients with sickle cell diseases, and a compensatory increase of RBC production occurs. During aplastic crisis, the reticulocyte count falls, causing rapid development of severe anemia. Mortality rates associated with both sequestration and aplastic crises are significant, and these conditions must be treated aggressively with volume administration and RBC transfusion.

Sickle cell disease can cause a functional asplenia with increased susceptibility to severe bacterial infections, especially with encapsulated organisms. An infection should therefore be suspected early and treated aggressively in patients with sickle cell disease.

Preventive measures must also be used if possible. In particular, patients with sickle cell disease should be monitored in the PICU after significant surgery—the goals being to prevent dehydration and hypoxemia, provide optimal analgesia, and maintain the hematocrit between 30% and 35%.

Red Blood Cell Transfusion

The management of anemia in critically ill patients is discussed in Chapters 19 and 150; this includes prevention of blood loss, transfusion of blood products, and administration of folic acid and iron. Prophylactic erythropoietin use has not been evaluated in large pediatric trials, but its utility appears questionable insofar as most RBC transfusions are received during the first few days after admission.^2,10

The risks and benefits of RBC transfusion are not similar in adults and children. Necrotizing enterocolitis in neonates¹¹ or erythrocyte alloimmunization in young girls (up to 8% of patients)¹² are significant problems in pediatric patients. RBC transfusion to neonates increases the ratio of adult to fetal Hb, which decreases the affinity of blood for oxygen.¹³ Nevertheless, RBCs improve oxygen transport in critically ill children,^14–17 although the improvement in clinically significant outcomes remains to be determined. Large variation in transfusion practice was observed among pediatric intensivists,^18,19 reflecting the unidentified Hb threshold with the best risk/benefit ratio in critically ill children. Maintaining Hb above 5.0 g/dL in hospitalized pediatric patients decreases the risk of death.^20,21 In a large randomized clinical trial enrolling 637 patients in 19 PICUs, Lacroix et al.²² demonstrated that a transfusion strategy to maintain Hb above 7 g/dL was as safe as a strategy to maintain Hb above 9.5 g/dL in stable critically ill children. While the number of transfusions was much lower in the restrictive transfusion group, no difference was observed in mortality rate or occurrence of new organ dysfunction.²² These findings were not different in three planned a priori subgroup analyses of patients in sepsis,²³ in postsurgical patients,²⁴ or in patients admitted following cardiac surgery.²⁵ These data and the cohesiveness of all subgroup analyses strongly support limiting RBC transfusion to patients with Hb below 7.0 g/dL in stable conditions. More data are required to identify a threshold in patients with cardiorespiratory instability.

In pediatric patients, packed RBCs should be administered on a unit-by-unit basis to limit exposure to multiple donors. Packed RBCs are available in half-units (standard division) or in small units of 75 mL (Pedipak) for young children. Packed RBC units must be warmed to 37°C for infants or if the transfused volume exceeds 30% of blood volume.

Transfusion in the neonatal period, in children with immunodeficiency, or transfusion using blood donated by family members are situations at higher risk of transfusion-associated graft-versus-host disease²⁶; irradiated packed RBCs should be used in these conditions.

Respiratory System