The purpose of this study is to assess if hyperbaric oxygen (HBO) treatment in patients experiencing sickle cell crisis would produce a decrease in pain and decrease in hospital length of stay. Before starting the process of investigating this scientific question it is important to take a look back to see what previous studies and research has been done related to HBO and sickle cell disease. While doing this, several key literature pieces stand out. The first by Laszlo 1969 studied 5 sickle cell crisis patients and the effects HBO had on sickling and assessed for clinical symptom resolution. It was found that HBO did reduce reversible sickled cells and persisted for some time after treatment. In regards to clinical symptomatic relief, one patient had complete resolution of his associated hematuria and another had complete pain relief after HBO treatment. This study showed that HBO can reverse sickling and may have some clinical benefit, but this study was small (N=5) and was not randomized.

In 1971 Reynolds published a case report of a patient with refractory painful crisis who was successfully treated with HBO. This patient was initially given blood, 5 liters per minute (LPM) oxygen therapy, fluid resuscitation, bicarbonate, and pain medications, and experienced no symptomatic relief. The patient was then treated with HBO and was found to be pain free afterwards. This case study was only one patient , but does give good reason to look into the possible benefit from HBO in the treatment of refractory sickle cell pain crisis. In a study by Embury in 1984, they followed 3 sickle cell patients who were treated with continuous O2 for 5 days. It was noted that during the oxygen treatment these patients had a reduction in erythropoetin, reduced irreversibly sickled cells and increase anemia. After treatment cessation, the patients then experienced a rebound increase in white blood cells (WBC) and Irreversibly sickled cells counts. It was also noted that 2 of the 3 patients had a painful crisis after completion of O2 therapy. This study suggests that oxygen may be beneficial on a short term basis, but prolonged exposure may be harmful. HBO was not used in this study, but serves as a possible reason to limit HBO treatments to a responsible number of treatments. In addition, it raises the question that if WBCs have a role in vaso-occlusive crisis (VOC) as this study suggestions, could HBOs known effect of leukocyte adhesion reductions play a role in mitigating this WBC increase? Zipursky (1992) studied the potential of oxygen therapy to reverse sickling in sickle cell disease. 50% oxygen delivered via venture mask was shown to reduce the number of reversible sickled cells but not irreversible sickled cells. During this time, some patients reported subjective symptomatic improvement, but not all. This study focused more on the objective number of reversibly sickled cells (RSC) and ISC pre and post oxygen therapy and not pain relief though.

Because this study showed reduced sickling it is implicated that HBO may both reduce sickling as well as provide symptomatic relief. In vitro effects of HBO on sickled cells were studied by Mychaskiw in 2001, which looked at the possibly of reversing sickling in vitro in a hyperbaric chamber. Blood samples from 10 patients with sickle cell disease were left at room air for 2 hours to allow to sickling and then underwent HBO treatment. When compared with controls, there was no effect from HBO on the morphology of the sickled cells. This study is a good direct look at in vitro cellular effects of HBO on sickled cells, yet other in vivo study results contradict this. In a study in 2012, Stirnemann looked at 9 patients who were in refractory VOC crisis and assessed their pain use as well as narcotic usage before and after HBO treatment. All 9 patients experienced pain reduction and decrease in morphine usage as a result of HBO therapy. This study took a direct look at VOC and HBO therapy, which suggest that HBO seems to be a viable option of VOC patients who are refractory to conventional therapy, but an N=9 is still a small sample size to draw a generalized conclusion about.

From this scholarly literature, many results suggest and point to the hypothesis that HBO may help ameliorate symptoms and have positive effects for sickle cell patients. However, no information has been gathered to date about how this may effect hospital length of stay. In addition, although a few studies did discuss pain reduction associated with HBO therapy, they are currently conflicting and all have too small of sample size to carry any weight when compared against each other. With the currently proposed research, it is a hope that a larger sample size be collected to help generalize this information to more patients.

Currently at University of Nebraska Medical Center (UNMC) and Nebraska Medicine, if a patient is identified as having sickle cell and experiencing an uncomplicated pain crisis that is not responding to acute treatment in the emergency department over the course of a few hours, that patient will be admitted to our hematology service. They will then continue to receive IV fluid administration, oxygen, and usually large doses of pain medications, until their pain subsides. Patient's labs such as complete blood count (CBC) and comprehensive metabolic panel (CMP) are monitored during this time for any acute changes. Once the patient's pain has subsided and no signs of complications such as infection, etc. are found, the patient is discharged with follow up in hematology clinic.